Melissa L Knothe Tate
@blueinnovatios.org
Professor
Blue Mountains World Interdisciplinary Innovation Institute
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Lucy Ngo and Melissa L. Knothe Tate
Springer Science and Business Media LLC
AbstractMolecular transport between the circulatory and musculoskeletal systems regulates articular joint physiology in health and disease. Osteoarthritis (OA) is a degenerative joint disease linked to systemic and local inflammation. Inflammatory events involve cytokines, which are secreted by cells of the immune system and modulate molecular transport across tissue interfaces (referred to as tight junction [TJ] barrier function). In a previous study from our group, OA knee joint tissues were shown to exhibit size separation of different sized molecules delivered as a single bolus to the heart (Ngo et al. in Sci. Rep. 8:10254, 2018). Here, in a follow up study of parallel design, we test the hypothesis that two common cytokines, with multifaceted roles in the etiology of osteoarthritis as well as immune state in general, modulate the barrier function properties of joint tissue interfaces. Specifically, we probe the effect of an acute cytokine increase (spike) on molecular transport within tissues and across tissue interfaces of the circulatory and musculoskeletal systems. A single bolus of fluorescent-tagged 70 kDa dextran, was delivered intracardially, either alone, or with either the pro-inflammatory cytokine TNF-α or the anti-inflammatory cytokine TGF-β, to skeletally mature (11 to 13-month-old) guinea pigs (Dunkin-Hartley, a spontaneous OA animal model). After five minutes' circulation, whole knee joints were serial sectioned and fluorescent block face cryo-imaged at near-single-cell resolution. The 70 kDa fluorescent-tagged tracer is analogous in size to albumin, the most prevalent blood transporter protein, and quantification of tracer fluorescence intensity gave a measure of tracer concentration. Within five minutes, a spike (acute doubling) in circulating cytokines TNF-α or TGF-β significantly disrupted barrier function between the circulatory and musculoskeletal systems, with barrier function essentially abrogated in the TNF-α group. In the entire volume of the joint (including all tissue compartments and the bounding musculature), tracer concentration was significantly decreased in the TGF-β- and TNF-α- compared to the control-group. These studies implicate inflammatory cytokines as gatekeepers for molecular passage within and between tissue compartments of our joints and may open new means to delay the onset and mitigate the progression of degenerative joint diseases such as OA, using pharmaceutical and/or physical measures.
Vina D. L. Putra, Kristopher A. Kilian, and Melissa L. Knothe Tate
Springer Science and Business Media LLC
AbstractAcross complex, multi-time and -length scale biological systems, redundancy confers robustness and resilience, enabling adaptation and increasing survival under dynamic environmental conditions; this review addresses ubiquitous effects of cytoskeletal remodelling, triggered by biomechanical, biophysical and biochemical cues, on stem cell mechanoadaptation and emergent lineage commitment. The cytoskeleton provides an adaptive structural scaffold to the cell, regulating the emergence of stem cell structure-function relationships during tissue neogenesis, both in prenatal development as well as postnatal healing. Identification and mapping of the mechanical cues conducive to cytoskeletal remodelling and cell adaptation may help to establish environmental contexts that can be used prospectively as translational design specifications to target tissue neogenesis for regenerative medicine. In this review, we summarize findings on cytoskeletal remodelling in the context of tissue neogenesis during early development and postnatal healing, and its relevance in guiding lineage commitment for targeted tissue regeneration. We highlight how cytoskeleton-targeting chemical agents modulate stem cell differentiation and govern responses to mechanical cues in stem cells’ emerging form and function. We further review methods for spatiotemporal visualization and measurement of cytoskeletal remodelling, as well as its effects on the mechanical properties of cells, as a function of adaptation. Research in these areas may facilitate translation of stem cells’ own healing potential and improve the design of materials, therapies, and devices for regenerative medicine.
Theatin van Leeuwen, Rhiannon P. Kuchel, Melissa L. Knothe Tate, and Per B. Zetterlund
Elsevier BV
Melissa L. Knothe Tate, Abhilash Srikantha, Christian Wojek, and Dirk Zeidler
Frontiers Media SA
“Brainless” cells, the living constituents inhabiting all biological materials, exhibit remarkably smart, i.e., stimuli-responsive and adaptive, behavior. The emergent spatial and temporal patterns of adaptation, observed as changes in cellular connectivity and tissue remodeling by cells, underpin neuroplasticity, muscle memory, immunological imprinting, and sentience itself, in diverse physiological systems from brain to bone. Connectomics addresses the direct connectivity of cells and cells’ adaptation to dynamic environments through manufacture of extracellular matrix, forming tissues and architectures comprising interacting organs and systems of organisms. There is imperative to understand the physical renderings of cellular experience throughout life, from the time of emergence, to growth, adaptation and aging-associated degeneration of tissues. Here we address this need through development of technological approaches that incorporate cross length scale (nm to m) structural data, acquired via multibeam scanning electron microscopy, with machine learning and information transfer using network modeling approaches. This pilot case study uses cutting edge imaging methods for nano- to meso-scale study of cellular inhabitants within human hip tissue resected during the normal course of hip replacement surgery. We discuss the technical approach and workflow and identify the resulting opportunities as well as pitfalls to avoid, delineating a path for cellular connectomics studies in diverse tissue/organ environments and their interactions within organisms and across species. Finally, we discuss the implications of the outlined approach for neuromechanics and the control of physical behavior and neuromuscular training.
Lucy Ngo and Melissa L. Knothe Tate
American Chemical Society (ACS)
Osteoarthritis (OA) is the fourth leading cause of disability in adults. Yet, few viable pharmaceutical options exist for pain abatement and joint restoration, aside from joint replacement at late and irreversible stages of the disease. From the first onset of OA, as joint pain increases, individuals with arthritis increasingly reach for drug delivery solutions, from taking oral glycosaminoglycans (GAGs) bought over the counter from retail stores (e.g., Costco) to getting injections of viscous, GAG-containing synovial fluid supplement in the doctor's office. Little is known regarding the efficacy of delivery mode and/or treatment by such disease-modulating agents. This Review addresses the interplay of mechanics and biology on drug delivery to affected joints, which has profound implications for molecular transport in joint health and (patho)physiology. Multiscale systems biology approaches lend themselves to understand the relationship between the cell and joint health in OA and other joint (patho)physiologies. This Review first describes OA-related structural and functional changes in the context of the multilength scale anatomy of articular joints. It then summarizes and categorizes, by size and charge, published molecular transport studies, considering changes in permeability induced through inflammatory pathways. Finally, pharmacological interventions for OA are outlined in the context of molecular weights and modes of drug delivery. Taken together, the current state-of-the-art points to a need for new drug delivery strategies that harness systems-based interactions underpinning molecular transport and maintenance of joint structure and function at multiple length scales from molecular agents to cells, tissues, and tissue compartments which together make up articular joints. Cutting edge and cross-length and -time scale imaging represents a key discovery enabling technology in this process.
Melissa Louise Knothe Tate
Frontiers Media SA
Life is mechanobiological. Natural living materials exhibit remarkable, emergent and smart properties under mechanical loading. Such materials are classified as mechanoactive, in contrast to electroactive polymers and materials that exhibit advanced properties when subjected to electrical stimulation. Cutting edge, multiscale imaging technologies have proven enabling for the elucidation of molecular to meso-scale structure and function of natural mechanoactive materials. Using Microscopy-Aided Design And ManufacturE, (MADAME) this perspective article describes mechanoactive properties of natural materials including skin-on-bones (periosteum) and bone itself. In so doing, it demonstrates the principle to emulate natural smart properties using recursive logic, the basis of many computer algorithms, and to design and manufacture mechanoactive materials and products using advanced manufacturing methods that also incorporate principles of recursive logic. In sum, the MADAME approach translates physically the computer science paradigm of recursion by implementing Jacquard textile methods, which themselves form a historical basis for computing machines, together with additive manufacturing methods including multidimensional printing, stereolithography, laser sintering, etc. These integrated methods provide a foundation and translational pathway for scaled-up manufacture of disruptive mechanoactive materials that will find use in fields as varied as medicine, safety, transport and sports, for internal (implants) and external (wearables) applications.
Joanna L. Ng, Vina D.L. Putra, and Melissa L. Knothe Tate
Elsevier BV
Vina D. L. Putra, Min Jae Song, Sarah McBride-Gagyi, Hana Chang, Kate Poole, Renee Whan, David Dean, Vittorio Sansalone, and Melissa L. Knothe Tate
Frontiers Media SA
Mechanomics represents the natural progression of knowledge at the intersection of mechanics and biology with the aim to codify the role of mechanical environment on biological adaptation. Compared to the mapping of the human genome, the challenge of mapping the mechanome remains unsolved. Solving this grand challenge will require both top down and bottom up R&D approaches using experimental and computational tools to visualize and measure adaptation as it occurs. Akin to a mechanical test of a smart material that changes its mechanical properties and local environment under load, stem cells adapt their shape, cytoskeletal architecture, intrinsic mechanical properties, as well as their own niche, through cytoskeletal adaptation as well as up- and down-regulation of structural proteins that modulate their mechanical milieux. Recent advances in live cell imaging allow for unprecedented study and measurements of displacements, shape and volume changes in stem cells, reconfiguring of cytoskeletal machinery (nucleus, cytoskeleton), in response to controlled mechanical forces and stresses applied at cellular boundaries. Coupled with multiphysics computational and virtual power theoretical approaches, these novel experimental approaches enable mechanical testing of stem cells, multicellular templates, and tissues inhabited by stem cells, while the stem cells themselves evolve over time. The novel approach is paving the way to decipher mechanisms of structural and functional adaptation of stem cells in response to controlled mechanical cues. This mini-review outlines integrated approaches and methodologies implemented to date in a series of studies carried out by our consortium. The consortium’s body of work is described in context of current roadblocks in the field and innovative, breakthrough solutions and is designed to encourage discourse and cross disciplinary collaboration in the scientific community.
Vina Putra, Iman Jalilian, Madeline Campbell, Kate Poole, Renee Whan, Florence Tomasetig, and Melissa Knothe Tate
Bio-Protocol, LLC
Mechanomics, the mechanics equivalent of genomics, is a burgeoning field studying mechanical modulation of stem cell behavior and lineage commitment. Analogous to mechanical testing of a living material as it adapts and evolves, mapping of the mechanome necessitates the development of new protocols to assess changes in structure and function in live stem cells as they adapt and differentiate. Previous techniques have relied on imaging of cellular structures in fixed cells and/or live cell imaging of single cells with separate studies of changes in mechanical and biological properties. Here we present two complementary protocols to study mechanobiology and mechanoadaptation of live stem cells in adherent and motile contexts. First, we developed and tested live imaging protocols for simultaneous visualization and tracking of actin and tubulin mechanoadaptation as well as shape and volume of cells and their nuclei in adherent model embryonic murine mesenchymal stem cells (C3H/10T1/2) and in a neuroblastoma cell line. Then we applied the protocol to enable quantitative study of primary human mesenchymal stem cells in a motile state, e.g., ingression in a three-dimensional, in vitro cell culture model. Together, these protocols enable study of emergent structural mechanoadaptation of the cell's own cytoskeletal machinery while tracking lineage commitment using phenotypic (quantitative morphology measures) and genotypic (e.g., reverse transcription Polymerase Chain Reaction, rtPCR) methods. These tools are expected to facilitate the mapping of the mechanome and incipient mechanistic understanding of stem cell mechanobiology, from the cellular to the tissue and organ length scales.
Joanna L. Ng, Tegtaranjit Singh, Lawrence C. Kwan, and Melissa L. Knothe Tate
Elsevier BV
Lucy Ngo, Anton Nathanson, Tomasz Garbowski, Ulf Knothe, Dirk Zeidler, and Melissa Knothe Tate
Bio-Protocol, LLC
Multibeam scanning electron microscopy (multiSEM) provides a technical platform for seamless nano-to-mesoscale mapping of cells in human tissues and organs, which is a major new initiative of the U.S. National Institutes of Health. Such cross-length-scale imaging is expected to provide unprecedented understanding of relationships between cellular health and tissue-organ as well as organismal-scale health outcomes. For example, understanding relationships between loss in cell viability and cell network connectivity enables identification of emergent behaviors and prediction of degenerative disease onset, in organs as diverse as bone and brain, at early timepoints, providing a basis for future treatments and prevention. Developed for rapid throughput imaging of minute defects on semiconductor wafers, multiSEM has recently been adapted for imaging of human organs, their constituent tissues, and their respective cellular inhabitants. Through integration of geospatial approaches, statistical and network modelling, advances in computing and the management of immense datasets, as well as recent developments in machine learning that enable the automation of big data analyses, multiSEM and other cross- cutting imaging technologies have the potential to exert a profound impact on elucidation of disease mechanisms, translating to improvements in human health. Here we provide a protocol for acquisition and preparation of sample specimen sizes of diagnostic relevance for human anatomy and physiology. We discuss challenges and opportunities to integrate this approach with multibeam scanning electron microscopy workflows as well as multiple imaging modalities for mapping of organ and tissue structure and function.
Daniel J. Hageman, Shuying Wu, Daniel Latimer, Karen Virdi, Chun H. Wang, and Melissa L. Knothe Tate
Elsevier BV
Lucy Ngo, Lillian E. Knothe, and Melissa L. Knothe Tate
Springer Science and Business Media LLC
AbstractThe role of molecular size selectivity in the onset and progression of osteoarthritis (OA), a degenerative disease of the musculoskeletal system and the most common cause of disability in aging adults, is unknown. Here we delivered a mixture of Texas-red (70 kDa), and Rhodamine-green (10 kDa) tagged, dextrans of neutral charge in a single bolus via heart injection to middle aged (8–10 months) and aged (17–19 months) Dunkin-Hartley Guinea pigs, a natural model for OA. We quantified tracer transport in serial-sectioned, cryofixed block specimens after five minutes’ circulation. A remarkable separation of the molecules was observed in serial fluorescent images of whole joint sections. The larger, 70 kDa red tracer was abundant in the marrow cavity albeit less prevalent or absent in the bone, cartilage, meniscus and other tissues of the joint. Tissues of the meniscus, ligament, and tendon exhibited abundant 10 kDa tracer; volumes of tissue containing this molecular tracer were significantly lower in older than in younger animals. Surprisingly, muscle fiber bundles exhibited little fluorescence, while their bounding fasciae fluoresced either red or green. Small caliber channels through the articular cartilage appeared to show a degree of green fluorescence not observed in the surrounding cartilage matrix. This study opens up new avenues for study of musculoskeletal physiology in health and disease as well as new strategies for drug delivery.
Daniel J. Hageman, Shuying Wu, Sharon Kilbreath, Stanley G. Rockson, Chun Wang, and Melissa L. Knothe Tate
Elsevier BV
Hans Jörg Sidler, Jacob Duvenage, Eric J. Anderson, Joanna Ng, Daniel J. Hageman, and Melissa L. Knothe Tate
Frontiers Media SA
Natural materials exhibit smart properties including gradients in biophysical properties that engender higher order functions, as well as stimuli-responsive properties which integrate sensor and/or actuator capacities. Elucidation of mechanisms underpinning such smart material properties (i), and translation of that understanding (ii), represent two of the biggest challenges in emulating natural design paradigms for design and manufacture of disruptive materials, parts, and products. Microscopy Aided Design And ManufacturE (MADAME) stands for a computer-aided additive manufacturing platform that incorporates multidimensional (multi-D) printing and computer-controlled weaving. MADAME enables the creation of composite design motifs emulating e.g., patterns of woven protein fibers as well as gradients in different caliber porosities, mechanical, and molecular properties, found in natural tissues, from the skin on bones (periosteum) to tree bark. Insodoing, MADAME provides a means to manufacture a new genre of smart materials, products and replacement body parts that exhibit advantageous properties both under the influence of as well as harnessing dynamic mechanical loads to activate material properties (mechanoactive properties). This Technical Report introduces the MADAME technology platform and its associated machine-based workflow (pipeline), provides basic technical background of the novel technology and its applications, and discusses advantages and disadvantages of the approach in context of current 3 and 4D printing platforms.
Joanna L. Ng, Ciara E. Collins, and Melissa L. Knothe Tate
Elsevier BV
Joanna L. Ng, Mariana E. Kersh, Sharon Kilbreath, and M. Knothe Tate
Frontiers Media SA
Life is mechanobiological: mechanical stimuli play a pivotal role in the formation of structurally and functionally appropriate body templates through mechanobiologically-driven cellular and tissue re/modeling. The body responds to mechanical stimuli engendered through physical movement in an integrated fashion, internalizing and transferring forces from organ, through tissue and cellular length scales. In the context of rehabilitation and therapeutic outcomes, such mechanical stimuli are referred to as mechanotherapy. Physical therapists use mechanotherapy and mechanical interventions, e.g., exercise therapy and manual mobilizations, to restore function and treat disease and/or injury. While the effect of directed movement, such as in physical therapy, is well documented at the length scale of the body and its organs, a number of recent studies implicate its integral effect in modulating cellular behavior and subsequent tissue adaptation. Yet the link between movement biomechanics, physical therapy, and subsequent cellular and tissue mechanoadaptation is not well established in the literature. Here we review mechanoadaptation in the context of physical therapy, from organ to cell scale mechanotransduction and cell to organ scale extracellular matrix genesis and re/modeling. We suggest that physical therapy can be developed to harness the mechanosensitivity of cells and tissues, enabling prescriptive definition of physical and mechanical interventions to enhance tissue genesis, healing, and rehabilitation.
Joanna L. Ng, Lillian E. Knothe, Renee M. Whan, Ulf Knothe, and Melissa L. Knothe Tate
Springer Science and Business Media LLC
AbstractWe are literally the stuff from which our tissue fabrics and their fibers are woven and spun. The arrangement of collagen, elastin and other structural proteins in space and time embodies our tissues and organs with amazing resilience and multifunctional smart properties. For example, the periosteum, a soft tissue sleeve that envelops all nonarticular bony surfaces of the body, comprises an inherently “smart” material that gives hard bones added strength under high impact loads. Yet a paucity of scalable bottom-up approaches stymies the harnessing of smart tissues’ biological, mechanical and organizational detail to create advanced functional materials. Here, a novel approach is established to scale up the multidimensional fiber patterns of natural soft tissue weaves for rapid prototyping of advanced functional materials. First second harmonic generation and two-photon excitation microscopy is used to map the microscopic three-dimensional (3D) alignment, composition and distribution of the collagen and elastin fibers of periosteum, the soft tissue sheath bounding all nonarticular bone surfaces in our bodies. Then, using engineering rendering software to scale up this natural tissue fabric, as well as multidimensional weaving algorithms, macroscopic tissue prototypes are created using a computer-controlled jacquard loom. The capacity to prototype scaled up architectures of natural fabrics provides a new avenue to create advanced functional materials.
Nicole Y.C. Yu, Connor A. O’Brien, Iveta Slapetova, Renee M. Whan, and Melissa L. Knothe Tate
Oxford University Press (OUP)
Abstract The periosteum, a composite cellular connective tissue, bounds all nonarticular bone surfaces. Like Velcro, collagenous Sharpey's fibers anchor the periosteum in a prestressed state to the underlying bone. The periosteum provides a niche for mesenchymal stem cells. Periosteal lifting, as well as injury, causes cells residing in the periosteum (PDCs) to change from an immobile, quiescent state to a mobile, active state. The physical cues that activate PDCs to home to and heal injured areas remain a conundrum. An understanding of these cues is key to unlocking periosteum's remarkable regenerative power. We hypothesized that changes in periosteum's baseline stress state modulate the quiescence of its stem cell niche. We report, for the first time, a three-dimensional, high-resolution live tissue imaging protocol to observe and characterize ovine PDCs and their niche before and after release of the tissue's endogenous prestress. Loss of prestress results in abrupt shrinkage of the periosteal tissue. At the microscopic scale, loss of prestress results in significantly increased crimping of collagen of periosteum's fibrous layer and a threefold increase in the number of rounded nuclei in the cambium layer. Given the body of published data describing the relationships between stem cell and nucleus shape, structure and function, these observations are consistent with a role for mechanics in the modulation of periosteal niche quiescence. The quantitative characterization of periosteum as a stem cell niche represents a critical step for clinical translation of the periosteum and periosteum substitute-based implants for tissue defect healing.
Shannon R. Moore, Céline Heu, Nicole Y.C. Yu, Renee M. Whan, Ulf R. Knothe, Stefan Milz, and Melissa L. Knothe Tate
Oxford University Press (OUP)
Abstract An abundance of surgical studies during the past 2 centuries provide empirical evidence of periosteum's regenerative power for reconstructing tissues as diverse as trachea and bone. This study aimed to develop quantitative, efficacy-based measures, thereby providing translational guidelines for the use of periosteum to harness the body's own healing potential and generate target tissues. The current study quantitatively and qualitatively demonstrated tissue generation modulated by a periosteum substitute membrane that replicates the structural constituents of native periosteum (elastin, collagen, progenitor cells) and its barrier, extracellular, and cellular properties. It shows the potentiation of the periosteum's regenerative capacity through the progenitor cells that inhabit the tissue, biological factors intrinsic to the extracellular matrix of periosteum, and mechanobiological factors related to implant design and implementation. In contrast to the direct intramembranous bone generated in defects surrounded by patent periosteum in situ, tissue generation in bone defects bounded by the periosteum substitute implant occurred primarily via endochondral mechanisms whereby cartilage was first generated and then converted to bone. In addition, in defects treated with the periosteum substitute, tissue generation was highest along the major centroidal axis, which is most resistant to prevailing bending loads. Taken together, these data indicate the possibility of designing modular periosteum substitute implants that can be tuned for vectorial and spatiotemporal delivery of biological agents and facilitation of target tissue genesis for diverse surgical scenarios and regenerative medicine approaches. It also underscores the potential to develop physical therapy protocols to maximize tissue genesis via the implant's mechanoactive properties. Significance In the past 2 centuries, the periosteum, a niche for stem cells and super-smart biological material, has been used empirically in surgery to repair tissues as diverse as trachea and bone. In the past 25 years, the number of articles indexed in PubMed for the keywords “periosteum and tissue engineering” and “periosteum and regenerative medicine” has burgeoned. Yet the biggest limitation to the prescriptive use of periosteum is lack of easy access, giving impetus to the development of periosteum substitutes. Recent studies have opened up the possibility to bank periosteal tissues (e.g., from the femoral neck during routine resection for implantation of hip replacements). This study used an interdisciplinary, quantitative approach to assess tissue genesis in modular periosteum substitute implants, with the aim to provide translational strategies for regenerative medicine and tissue engineering.
André F. Pereira, Daniel J. Hageman, Tomasz Garbowski, Christof Riedesel, Ulf Knothe, Dirk Zeidler, and Melissa L. Knothe Tate
Public Library of Science (PLoS)
Multi-beam scanning electron microscopy (mSEM) enables high-throughput, nano-resolution imaging of macroscopic tissue samples, providing an unprecedented means for structure-function characterization of biological tissues and their cellular inhabitants, seamlessly across multiple length scales. Here we describe computational methods to reconstruct and navigate a multitude of high-resolution mSEM images of the human hip. We calculated cross-correlation shift vectors between overlapping images and used a mass-spring-damper model for optimal global registration. We utilized the Google Maps API to create an interactive map and provide open access to our reconstructed mSEM datasets to both the public and scientific communities via our website www.mechbio.org. The nano- to macro-scale map reveals the tissue’s biological and material constituents. Living inhabitants of the hip bone (e.g. osteocytes) are visible in their local extracellular matrix milieu (comprising collagen and mineral) and embedded in bone’s structural tissue architecture, i.e. the osteonal structures in which layers of mineralized tissue are organized in lamellae around a central blood vessel. Multi-beam SEM and our presented methodology enable an unprecedented, comprehensive understanding of health and disease from the molecular to organ length scale.
Melissa L. Knothe Tate, Peter W. Gunning, and Vittorio Sansalone
Informa UK Limited
ABSTRACT Stem cell “mechanomics” refers to the effect of mechanical cues on stem cell and matrix biology, where cell shape and fate are intrinsic manifestations of form and function. Before specialization, the stem cell itself serves as a sensor and actuator; its structure emerges from its local mechanical milieu as the cell adapts over time. Coupling of novel spatiotemporal imaging and computational methods allows for linking of the energy of adaptation to the structure, biology and mechanical function of the cell. Cutting edge imaging methods enable probing of mechanisms by which stem cells' emergent anisotropic architecture and fate commitment occurs. A novel cell-scale model provides a mechanistic framework to describe stem cell growth and remodeling through mechanical feedback; making use of a generalized virtual power principle, the model accounts for the rate of doing work or the rate of using energy to effect the work. This coupled approach provides a basis to elucidate mechanisms underlying the stem cell's innate capacity to adapt to mechanical stimuli as well as the role of mechanoadaptation in lineage commitment. An understanding of stem cell mechanoadaptation is key to deciphering lineage commitment, during prenatal development, postnatal wound healing, and engineering of tissues.
Melissa L. Knothe Tate and Thomas Fath
Wiley
Cell health and cell network patency dictate human physical and mental health throughout life. Cutting edge multiscale imaging and mapping of cell to organ structure and function is unravelling the remarkable plasticity of cellular networks, from bone to brain. Insights from these studies will enable the development of next generation implants to replace, repair and reprogram cellular networks, for promotion of mental and physical health.
Melissa L. Knothe Tate, Dirk Zeidler, André F. Pereira, Daniel Hageman, Tomasz Garbowski, Sanjay Mishra, Lauren Gardner, and Ulf R. Knothe
Wiley
This study combines novel multibeam electron microscopy with a geographical information system approach to create a first, seamless, navigable anatomic map of the human hip and its cellular inhabitants. Using spatial information acquired by localizing relevant map landmarks (e.g. cells, blood vessels), network modeling will enable disease epidemiology studies in populations of cells inhabiting tissues and organs.
Melissa L. Knothe Tate, Michael Detamore, Jeffrey R. Capadona, Andrew Woolley, and Ulf Knothe
Elsevier BV