Soft connective tissues at steady state are dynamic; resident cells continually read environmental cues and respond to them to promote homeostasis, including maintenance of the mechanical properties of the extracellular matrix (ECM) that are fundamental to cellular and tissue health. The mechanosensing process involves assessment of the mechanics of the ECM by the cells through integrins and the actomyosin cytoskeleton, and is followed by a mechanoregulation process, which includes the deposition, rearrangement or removal of the ECM to maintain overall form and function. Progress towards understanding the molecular, cellular and tissue-level effects that promote mechanical homeostasis has helped to identify key questions for future research.

Mechanotransduction and extracellular matrix homeostasis

The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors

Mechanical forces play important roles in the regulation of various biological processes at the molecular and cellular level, such as gene expression, adhesion, migration, and cell fate, which are essential to the maintenance of tissue homeostasis. In this review, we discuss emerging bioengineered tools enabled by microscale technologies for studying the roles of mechanical forces in cell biology. In addition to traditional mechanobiology experimental techniques, we review recent advances of microelectromechanical systems (MEMS)-based approaches for cell mechanobiology and discuss how microengineered platforms can be used to generate in vivo–like micromechanical environment in in vitro settings for investigating cellular processes in normal and pathophysiological contexts. These capabilities also have significant implications for mechanical control of cell and tissue development and cell-based regenerative therapies.

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Microengineered Platforms for Cell Mechanobiology

Integrins in mechanotransduction

Non-Euclidean plates are a subset of the class of elastic bodies having no stress-free configuration. Such bodies exhibit residual stress when relaxed from all external constraints, and may assume complicated equilibrium shapes even in the absence of external forces. In this work we present a mathematical framework for such bodies in terms of a covariant theory of linear elasticity, valid for large displacements. We propose the concept of non-Euclidean plates to approximate many naturally formed thin elastic structures. We derive a thin plate theory, which is a generalization of existing linear plate theories, valid for large displacements but small strains, and arbitrary intrinsic geometry. We study a particular example of a hemispherical plate. We show the occurrence of a spontaneous buckling transition from a stretching dominated configuration to bending dominated configurations, under variation of the plate thickness.

http://www.ma.huji.ac.il/~razk/Publications/PDF/ESK08.pdf

Elastic theory of unconstrained non-Euclidean plates

Mechanical loads induce changes in the structure, composition, and function of living tissues. Cells in tissues are responsible for these changes, which cause physiological or pathological alterations in the extracellular matrix (ECM). This article provides an introductory review of the mechanobiology of load-sensitive cells in vivo, which include fibroblasts, chondrocytes, osteoblasts, endothelial cells, and smooth muscle cells. Many studies have shown that mechanical loads affect diverse cellular functions, such as cell proliferation, ECM gene and protein expression, and the production of soluble factors. Major cellular components involved in the mechanotransduction mechanisms include the cytoskeleton, integrins, G proteins, receptor tyrosine kinases, mitogen-activated protein kinases, and stretch-activated ion channels. Future research in the area of cell mechanobiology will require novel experimental and theoretical methodologies to determine the type and magnitude of the forces experienced at the cellular and sub-cellular levels and to identify the force sensors/receptors that initiate the cascade of cellular and molecular events

B P. Thampatty

Papers

An introductory review of cell mechanobiology.