Intermediate filament mechanics in vitro and in the cell: from coiled coils to filaments, fibers and networks

Abstract

Summary Intermediate filament proteins form filaments, fibers and networks both in the cytoplasm and the nucleus of metazoan cells. Their general structural building plan accommodates highly varying amino acid sequences to yield extended dimeric α-helical coiled coils of highly conserved design. These “rod” particles are the basic building blocks of intrinsically flexible, filamentous structures that are able to resist high mechanical stresses, i.e. bending and stretching to a considerable degree, both in vitro and in the cell. Biophysical and computer modeling studies are beginning to unfold detailed structural and mechanical insights into these major supramolecular assemblies of cell architecture, not only in the “test tube” but also in the cellular and tissue context.

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

“…The lateral association of four tetramers gener-ates so-called unit-length filaments (ULFs), which longitudinally coalesce into mature filaments with a propensity to bundle and organize into three-dimensional (3D) networks (Herrmann et al 2009;Koster et al 2015;Herrmann and Aebi, 2016). Keratins show extensive sequence diversity, a feature that discriminates them from actins and tubulins (Schweizer et al 2006;Fletcher and Mullins 2010).…”

“…The mechanical properties of epithelial cells largely depend on actin filaments, microtubules, and KIF (Fletcher and Mullins 2010;Koster et al 2015). Although the contribution of actin filaments and microtubules to these properties is well accepted, the contribution of keratins to the resilience of epithelia against various types of deformation remained unknown.…”

Keratin network modifications lead to the mechanical stiffening of the hair follicle fiber

“…An active field aims at understanding how the local structural and mechanical properties of bionetworks define its macroscopic mechanics from a molecular scale toward a cellular and tissue scale (4-6). One challenge is that the properties of these networks have to be considered over multiple length and force scales with macroscopic mechanical forces being transduced from the whole tissue scale down to the cellular and molecular level and vice versa.At the cellular level, the last decades witnessed for a considerable advancement toward a better understanding of how the cytoskeleton composed of actin, microtubules, and intermediate filaments (IFs) determines cellular mechanics (1,(6)(7)(8). In vitro studies on isolated cells (6) and reconstituted in vitro bionetworks with controllable architecture and composition (9-12) considerably advanced our knowledge of cytoskeletal mechanics.…”

“…At the cellular level, the last decades witnessed for a considerable advancement toward a better understanding of how the cytoskeleton composed of actin, microtubules, and intermediate filaments (IFs) determines cellular mechanics (1,(6)(7)(8). In vitro studies on isolated cells (6) and reconstituted in vitro bionetworks with controllable architecture and composition (9-12) considerably advanced our knowledge of cytoskeletal mechanics.…”

Investigating Cellular Nanoscale with X-rays

“…The cytoskeleton of eukaryotic cells is composed of three main structures [97]: i) the microfilaments made out of actin, having a diameter of 7 to 8 nm [60], ii) the microtubules made out of tubulin, which are hollow tubes with a diameter of 25 nm [98], and iii) the intermediate filaments (IFs) made out of various proteins, having a diameter of 10 nm [99,100]. Each of these three distinct structures have different roles in the cells.…”