This is the only single authored text on biological polymers available for bioengineering and biomedical engineering students. The book describes the structure of polymers and how these molecules are put together to make the tissues of the body and also their role in surgical implants and in structural diseases. It provides essential reading for biomedical engineers, biologists, physicians, health care professionals and other biomedical researchers who are interested in understanding how physical forces affect the biology, physiology and pathophysiology of humans. The author is an expert on the effect of mechanical forces on extracellular matrix.

The extracellular matrix (ECM) provides structural support to tissues, while exerting biochemical and mechanical signals to resident cells. Such mechanical signals, the most familiar being matrix stiffness, regulate cell morphology, differentiation, migration, proliferation and gene expression. Therefore, studying the mechanical properties of the extracellular matrix is crucial to understanding cell behavior. With collagen type I being the most abundant protein found in mammalian tissues, prior works have studied its mechanical properties at the macroscale and reported a strong deviation from linear elasticity, exhibiting strain stiffening and compression weakening behavior. However, to better understand cell-matrix interactions more information about the matrix at the length scale of a cell is needed. Here we design an experimental method to quantify matrix stiffness at the length scale of a cell while accounting for matrix nonlinearity. We use spherical particles made of an active hydrogel that contract when heated, mimicking cell contraction. Results showed that the matrix stiffness is highly heterogeneous at the length scale of a cell, with values ranging by a factor of 3. Next, we examine the effect of matrix heterogeneity in structure on cell ability to sense other stiffer inclusions in the matrix, such as ducts, tumors or regions of abnormally high stiffness. Using a combination of experiments and modeling, we determine the extent to which matrix heterogeneity disrupts cell sensing of a locally stiff feature in the matrix. We found that the propagation of mechanical cues through the matrix depends on length scale, with single cells able to sense only the stiffness of the nearby fibers and multicellular structures, such as tumors, also sensing the stiffness of distant matrix features. Lastly, another matrix component, hyaluronic acid, is incorporated in our experiments to test its effect on fibrous collagen mechanics at the length scale of a cell. The addition of hyaluronic acid was found to make displacements in fibrous collagen to decay faster with distance from localized loads, closer to linear elasticity prediction, indicating a more linear matrix behavior with less compression softening. Also, collagen-hyaluronic acid matrices decrease the ability of fibrous collagen to hold permanent displacements, creating a more elastic matrix. By applying these findings to study matrix remodeling due to localized forces, we found that hyaluronic acid partially--but not fully--inhibited matrix remodeling. These results are evidence that there must be another mechanism for mechanical remodeling, which provides new experimental evidence supporting prior working showing that mechanical remodeling can be described by a phase transition associated with instability caused by compression softening. Overall, the findings of this thesis highlight the importance of length scale when trying to understand cell-matrix interactions. Small changes in local matrix structure can result in different behavior of neighboring cells, highlighting the importance of local matrix mechanics in understanding cell behavior in normal or diseased tissues.

Not only does this book provide a comprehensive review of current research advances in collagen structure and mechanics, it also explores this biological macromolecule’s many applications in biomaterials and tissue engineering. Readers gain an understanding of the structure and mechanical behavior of type I collagen and collagen-based tissues in vertebrates across all length scales, from the molecular (nano) to the organ (macro) level.

Explores a Range of Multiscale Biomechanics/Mechanobiology Concepts Cell and Matrix Mechanics presents cutting-edge research at the molecular, cellular, and tissue levels in the field of cell mechanics. This book involves key experts in the field, and covers crucial areas of cell and tissue mechanics, with an emphasis on the roles of mechanical forces in cell–matrix interactions. Providing material in each chapter that builds on the previous chapters, it effectively integrates length scales and contains, for each length scale, key experimental observations and corresponding quantitative theoretical models. Summarizes the Three Hierarchical Levels of Cell Mechanics The book contains 14 chapters and is organized into three sections. The first section focuses on the molecular level, the second section details mechanics at the cellular level, and the third section explores cellular mechanics at the tissue level. The authors offer a thorough description of the roles of mechanical forces in cell and tissue biology, and include specific examples. They incorporate descriptions of associated theoretical models, and provide the data and modeling framework needed for a multi-scale analysis. In addition, they highlight the pioneering studies in cell–matrix mechanics by Albert K. Harris. The topics covered include: The passive and active mechanical properties of cytoskeletal polymers and associated motor proteins along with the behavior of polymer networks The mechanical properties of the cell membrane, with an emphasis on membrane protein activation caused by membrane forces The hierarchical organization of collagen fibrils, revealing that a delicate balance exists between specific and nonspecific interactions to result in a structure with semicrystalline order as well as loose associations The roles of matrix mechanical properties on cell adhesion and function along with different mechanical mechanisms of cell–cell interactions The effects of mechanical loading on cell cytoskeletal remodeling, summarizing various modeling approaches that explain possible mechanisms regulating the alignment of actin stress fibers in response to stretching The mechanical testing of cell-populated collagen matrices, along with theory relating the passive and active mechanical properties of the engineered tissues Cell migration behavior in 3-D matrices and in collective cell motility The role of mechanics in cartilage development The roles of both cellular and external forces on tissue morphogenesis The roles of mechanical forces on tumor growth and cancer metastasis Cell and Matrix Mechanics succinctly and systematically explains the roles of mechanical forces in cell–matrix biology. Practitioners and researchers in engineering and physics, as well as graduate students in biomedical engineering and mechanical engineering related to mechanobiology, can benefit from this work.

Mechanobiology in Health and Disease brings together contributions from leading biologists, clinicians, physicists and engineers in one convenient volume, providing a unified source of information for researchers in this highly multidisciplinary area. Opening chapters provide essential background information on cell mechanotransduction and essential mechanobiology methods and techniques. Other sections focus on the study of mechanobiology in healthy systems, including bone, tendons, muscles, blood vessels, the heart and the skin, as well as mechanobiology studies of pregnancy. Final chapters address the nascent area of mechanobiology in disease, from the study of bone conditions, skin diseases and heart diseases to cancer. A discussion of future perspectives for research completes each chapter in the volume. This is a timely resource for both early-career and established researchers working on mechanobiology. Provides an essential digest of primary research from many fields and disciplines in one convenient volume Covers both experimental approaches and descriptions of mechanobiology problems from mathematical and numerical perspectives Addresses the hot topic of mechanobiology in disease, a particularly dynamic field of frontier science

This book describes the current state of knowledge in the field of multi-scale ECM mechanics and mechanobiology with a focus on experimental and modelling studies in biomechanical characterization, advanced optical microscopy and imaging, as well as computational modeling. This book also discusses the scale dependency of ECM mechanics, translation of mechanical forces from tissue to cellular level, and advances and challenges in improving our understanding of cellular mechanotransduction in the context of living tissues and organisms.

This book will cover the cutting-edge developments in molecular and cellular mechanobiology to date. Readers will have a clear understanding of mechanobiology at the molecular and cellular levels, encompassing the mechanosensors, transducers, and transcription. An integrative approach across different scales from molecular sensing to mechanotransduction and gene modulation for physiological regulation of cellular functions will be explored, as well as applications to pathophysiological states in disease. A comprehensive understanding of the roles of physicochemical microenvironment and intracellular responses in determining cellular function in health and disease will also be discussed.

Knowledge of the extracellular matrix (ECM) is essential to understand cellular differentiation, tissue development, and tissue remodeling. This volume of the series “Biology of Extracellular Matrix” provides a timely overview of the structure, regulation, and function of the major macromolecules that make up the extracellular matrix. It covers topics such as collagen types and assembly of collagen-containing suprastructures, basement membrane, fibronectin and other cell-adhesive glycoproteins, proteoglycans, microfibrils, elastin, fibulins and matricellular proteins, such as thrombospondin. It also explores the concept that ECM components together with their cell surface receptors can be viewed as intricate nano-devices that allow cells to physically organize their 3-D-environment. Further, the role of the ECM in human disease and pathogenesis is discussed as well as the use of model organisms in elucidating ECM function.

The objective of the presented research is to examine the relationship between the cellular microenvironment and biochemical response of metastatic cells. Clinically recognized as a trait of cancer progression, the cellular microenvironment can have variable and distinct mechanical properties that are processed via cellular mechanosensing, resulting in a cellular biochemical response. A range of studies investigating the interactions between the cellular micromechanical environment and the cell's molecular response during disease progression have been made, yet remain absent of quantitative characterization of many of these coordinated responses. The fundamental inquiry that drives the following research attempts to elucidate how a cell perceives the physical microenvironment and converts that signal to a biochemical response. With the goal of providing insight to such responses, the presented research seeks to elucidate the following questions: (1) What are the integrated effects of ECM stiffness, ECM architecture, and breast cancer cell metastatic potential on cell migration? (2) How does endogenous tissue transglutaminase (tTG) cross-linking of the ECM scaffold effect ECM mechanical properties? (3) How does the architecture and stiffness of the extracellular matrix (ECM) effect the systems-level cellular migration and signaling response? (4) What are the integrated effects of ECM architecture and the targeted knockdown of integrin [beta]1 and MT1-MMP on cellular metastatic potential? The presented research utilizes an interdisciplinary approach, integrating experimental mechanics, biochemical analysis, cellular biology techniques, covalent chemistry, and various microscopy techniques, to investigate these events. In short, cancerous cells are cultured atop or within synthetic collagen type I ECMs of varying mechanical stiffness and structure. These cells are subsequently analyzed by molecular analysis and immunoassays, including quantitative PCR, Western blotting, and gelatin zymography, to acquire measures of the cellular response to perturbations of micromechanical environment. Time-lapse microscopy experiments and subsequent image analyses enable observations of cellular migratory potential through synthetic ECMs. Results indicate that cooperative synergy between ECM properties, cell-matrix adhesion, and pericellular proteolysis drive cell migratory potential of highly invasive tumorigenic cell populations. Collectively, these findings contribute to the cancer biology and mechanobiology fields by systematically extending current insights of matrix mechanics, cellular signaling, and cellular migratory potential in cancer.