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      Biophysical Tools to Study Cellular Mechanotransduction

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          Abstract

          The cell membrane is the interface that volumetrically isolates cellular components from the cell’s environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane’s bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na +, Ca 2+, K + channels). The membrane’s biomechanical functions include sensing external forces and/or the rigidity of the external environment through force transmission, specific conformational changes and/or signaling through mechanoreceptors (e.g., platelet endothelial cell adhesion molecule (PECAM), vascular endothelial (VE)-cadherin, epithelial (E)-cadherin, integrin) embedded in the membrane. Certain mechanical stimulations through specific receptor complexes induce electrical and/or chemical impulses in cells and propagate across cells and tissues. These biomechanical sensory and biochemical responses have profound implications in normal physiology and disease. Here, we discuss the tools that facilitate the understanding of mechanosensitive adhesion receptors. This article is structured to provide a broad biochemical and mechanobiology background to introduce a freshman mechano-biologist to the field of mechanotransduction, with deeper study enabled by many of the references cited herein.

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          Most cited references206

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          Observation of a single-beam gradient force optical trap for dielectric particles

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            RGD and other recognition sequences for integrins.

            Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands. Some other integrins bind to related sequences in their ligands. The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. Reagents that bind selectively to only one or a few of the RGD-directed integrins can be designed by cyclizing peptides with selected sequences around the RGD and by synthesizing RGD mimics. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.
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              Local force and geometry sensing regulate cell functions.

              The shapes of eukaryotic cells and ultimately the organisms that they form are defined by cycles of mechanosensing, mechanotransduction and mechanoresponse. Local sensing of force or geometry is transduced into biochemical signals that result in cell responses even for complex mechanical parameters such as substrate rigidity and cell-level form. These responses regulate cell growth, differentiation, shape changes and cell death. Recent tissue scaffolds that have been engineered at the micro- and nanoscale level now enable better dissection of the mechanosensing, transduction and response mechanisms.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Bioengineering (Basel)
                Bioengineering (Basel)
                bioengineering
                Bioengineering
                MDPI
                2306-5354
                07 February 2017
                March 2017
                : 4
                : 1
                : 12
                Affiliations
                [1 ]Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA
                [2 ]Department of Mechanical Engineering and Energy Processes, Southern Illinois University Carbondale, Carbondale, IL 62901, USA
                [3 ]Department of Mechanical and Aerospace Engineering, Old Dominion University, Norfolk, VA 23529, USA
                Author notes
                [* ]Correspondence: ismaeelmuhamed@ 123456ncsu.edu (I.M.); farhan.chowdhury@ 123456siu.edu (F.C.); vmarutha@ 123456odu.edu (V.M.); Tel.: +1-919-515-8002 (I.M.); +1-618-453-7833 (F.C.); +1-757-683-4978 (V.M.)
                Article
                bioengineering-04-00012
                10.3390/bioengineering4010012
                5590431
                cbf1d652-9e69-4145-bc83-7215adc3f95e
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 October 2016
                : 02 February 2017
                Categories
                Review

                mechanotransduction,traction force microscopy,magnetic twisting cytometry,shear flow microfluidic device,integrins,focal adhesions,cadherins,adherens junction

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