Tensegrity-based mechanosensing from macro to micro

Abstract

This article is a summary of a lecture on cellular mechanotransduction that was presented at a symposium on "Cardiac Mechano-Electric Feedback and Arrhythmias" that convened at Oxford, England in April 2007. Although critical mechanosensitive molecules and cellular components, such as integrins, stretch-activated ion channels, and cytoskeletal filaments, have been shown to contribute to the response by which cells convert mechanical signals into a biochemical response, little is known about how they function in the structural context of living cells, tissues and organs to produce orchestrated changes in cell behavior in response to stress. Here, studies are reviewed that suggest our bodies use structural hierarchies (systems within systems) composed of interconnected extracellular matrix and cytoskeletal networks that span from the macroscale to the nanoscale to focus stresses on specific mechanotransducer molecules. A key feature of these networks is that they are in a state of isometric tension (i.e., experience a tensile prestress), which ensures that various molecular-scale mechanochemical transduction mechanisms proceed simultaneously and produce a concerted response. These features of living architecture are the same principles that govern tensegrity (tensional integrity) architecture, and mathematical models based on tensegrity are beginning to provide new and useful descriptions of living materials, including mammalian cells. This article reviews how the use of tensegrity at multiple size scales in our bodies guides mechanical force transfer from the macro to the micro, as well as how it facilitates conversion of mechanical signals into changes in ion flux, molecular binding kinetics, signal transduction, gene transcription, cell fate switching and developmental patterning.

Controlled two-photon photodegradation of PEG hydrogels to study and manipulate subcellular interactions on soft materials

“…12, 13 Mechanotransduction relays these physical signals via dynamic focal adhesion formation and cytoskeletal organization, which regulate cell morphology, proliferation, migration, differentiation, and apoptosis via changes in gene expression. 12, 14–16 …”

“…18 In short, cells exert contractile forces as they actively engage with the ECM introducing tensile stresses in the cytoskeleton that originate at focal adhesions and it is now evident that both dynamic adhesion and force generation play a major role in directing cell function. 14 …”

Perfluorocarbon induces alveolar epithelial cell response through structural and mechanical remodeling

“…This opens the road for future studies. One of these systems is the intracellular tensed actin structure which has already been proven to play a key role in mechanotransduction (Wang et al 1993;Ingber 2008). The other is the membranous glycocalyx layer which is known to play a role on the shear stress response of endothelial cells (Yao et al 2007) and is also present in alveolar epithelial cells (Martins and Abairos 2002).…”

“…In particular, we tested the roles of CSK prestress (by means of F-actin depolymerizing treatment by cytochalasin D (CytoD)) and glycocalyx layer (by means of glycocalyx degradation) which have already been shown to contribute to mechanotransduction as well as to intracellular and transmembrane remodeling in response to stress (Martins and Abairos 2002;Thi et al 2004;Féréol et al 2009;Ingber 2008).…”

Pancreatic carcinoma development: new etiological and pathogenetic evidence

“…Therefore, mechanical loads act as developmental regulators. 67,68 According to this model, cells may be considered as tensed structures that are resistant to shape distortion and that self stabilize by encompassing other supportive structures that counteract compression. Furthermore, cytoskeleton is directly associated with integrins, which represent specialized mechanoreceptors on the cellular surface.…”