Tensegrity architecture and the mammalian cell cytoskeleton

Abstract

Mechanotransduction the cellular response to mechanical stress is governed by the cytoskeleton (CSK), a molecular network composed of different types of biopolymers (microfilaments, microtubules and intermediate filaments) that mechanically stabilizes the cell and actively generates contractile forces. To carry out certain behaviors (e.g., crawling, spreading, division, invasion), cells must modify their CSK to become highly deformable, whereas in order to maintain their structural integrity when mechanically stressed, the CSK must behave like an elastic solid. These responses are governed by the passive material properties of the CSK, as well as stress-induced changes in biochemistry that modify the structure of the CSK. Although the mechanical properties of cells govern their form and function, and when abnormal, lead to a wide range of diseases, little is known about the molecular and biophysical basis of cell mechanics. Most of the existing engineering models of cells are ad hoc descriptions based on measurements obtained under particular experimental conditions, and these continuum models usually ignore contributions of subcellular structures and molecular components. Over two decades ago, we introduced a model of the cell based on tensegrity architecture which proposes that preexisting tensile stress in the CSK is critical for cell shape stability. Key to this model is the concept that this stabilizing tensile “prestress” results from a complementary force balance between multiple, discrete, molecular support elements, including microfilaments, intermediate filaments and microtubules in the CSK, as well as external adhesions to the extracellular matrix (ECM) and to neighboring cells. In this chapter, we review progress in the area of cellular tensegrity, including the mechanistic basis of the tensegrity model, and development of theoretical formulations of this model that have led to multiple a priori predictions relating to cell mechanical behaviors which have been confirmed in experimental studies with living cells. We describe how the CSK and ECM form a single, tensionally-integrated, structural system and how distinct molecular biopolymers of the CSK may bear either tensile or compressive loads inside the cell. The tensegrity model is also compared and contrasted with other models of cell mechanics. Taken together, these recent theoretical and experimental studies confirm that the cellular tensegrity model is a useful model because it provides a mechanism to link mechanics to structure at the molecular level, in addition to helping to explain how mechanical signals are transduced into biochemical responses within living cells and tissues.