Mechanical Regulation of Cells by Materials and Tissues
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Wendy E. Thomas, Dennis E. Discher, and V. Prasad Shastri Abstract Over the last dozen years, studies at the cell and tissue level have demonstrated that the function and fate of all cells, stem cells in particular, are affected by the collective physical properties of their microenvironments. Meanwhile, biophysical studies at the single molecule level have taught us a great deal about how mechanical forces affect the structure and function of proteins involved in the assembly of cells into tissues. Together, these molecular, cellular, and tissue studies provide insight into the process and importance of mechanotransduction, which is the process by which mechanical forces are transduced into biological signals. This insight should motivate biomimetic approaches to better control cell fate and tissue function.
Introduction: Cells Feel Their Environment Polymer physics has taught us that for a given chain chemistry, polymer molecular weight and cross-linking exert strong effects on the many physical properties of polymeric matter. Solid tissues in animals are no exception. Tissues are, of course, composed of highly hydrated natural polymers, especially proteins and carbohydrates, and elasticity (E) is one intrinsic physical property that seems well-controlled in many such tissues—particularly at the scale of cells. Recognition of this fact has combined over the last decade with an increasing recognition that cells also sense the elasticity of their microenvironments. Animal cells taken from solid tissues— such as neurons from brain, myocytes from muscle, or osteoblasts from bone—have long been known to require adhesion to a solid to be viable. Cells are said to be “anchorage dependent,” but a “solid” is a vague specification for any materials scientist. A solid can be soft or stiff, thick or thin, smooth or rough on its surface. In vivo, the solid perceived by a given cell could be an adjacent cell or it could be the extracellular matrix (ECM) that is composed of collagens plus other networking protein and carbohydrate chains that constitute the most abundant molecules in animals.
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Importantly, while a collagen molecule is a well-defined biochemical entity, its assembly into fibers of varied diameter and subsequent cross-linking with embellishment by other ECM molecules means that collagen is as inadequate a physical specification for biological use as polyester is for any synthetic application. From another perspective, cells lack eyes and ears, and if you were likewise blind and deaf, you would rely heavily on your sense of touch. You would feel a soft chair to sit on, a hard wall to avoid, or whether you were walking on carpet or concrete. Tissue cells also possess a sense of touch that allows them to determine where they
are and what they should be doing. Cells can push, protrude, and sterically interact with their surroundings, but their sense of touch appears mediated by attractive interactions with specific “adhesion” molecules that provide a means for cells to engage and actively pull on their surround
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