The biomechanical integrin

Abstract

The integrin lies at the center of our efforts to understand mechanotransduction in the human body. Over the past two decades, a wealth of information has yielded important insights into integrin structure and functioning in biochemical pathways; however, relatively little emphasis has been placed on mechanics. In this article, we review the current knowledge base of integrin mechanobiology by examining the role of integrins in stabilizing tissue structure, the mechanisms of integrin force transfer, the process of cell migration, and the pathology of cancer. In order to successfully address the gaps in cancer and other disease research going forward, future efforts of integrin mechanobiology must focus on examining cells in 3D environments and integrating our current understanding into computational models that predict the behavior of integrins in non-equilibrium interactions.

Figure 1

Illustration of a focal adhesion (FA). β subunits of activated integrins bind to ECM ligands on the extracellular side of the cell membrane, as well as both directly and indirectly to various mechanical anchorage and signaling proteins on the cytoplasmic side of the membrane. While determining FA composition comprises an active area of research, several of the most well understood FA constituent proteins are depicted. They include anchorage proteins talin, vinculin, paxillin, and α-actinin, as well as signaling proteins FAK, Src, and zyxin, which is a major component of a mature FA.

Figure 2

Illustration of cell traction forces (CTFs) generated during cell migration. Actin polymerization facilitates protrusion of the leading edge that is accompanied by traction forces exerted across nascent focal complexes and mature focal adhesions (Wiesner et al.) (Wiesner et al.). Forward protrusion in concert with contraction of the rear cell body overcomes ECM resistive adhesive tractions to allow forward cell migration.

Figure 3

Systems-level view of integrin mechanobiology. Over the past two decades, the study of integrins has largely been associated with structural and biochemical information. Although relatively little emphasis has been placed on integrin mechanobiology, recent strides have been made in elucidating the role of integrins in tissue structural maintenance, mechanotransduction, cell migration, and pathophysiology. In order to successfully navigate the complex landscape of diseases such as cancer, future efforts of integrin mechanobiology must focus on examining cells in 3D environments, accurately integrating the current knowledge base into computational models, and understanding the behavior of integrins in non-equilibrium interactions.