Abstract:

The mechanical properties of cells are essential in determining a myriad of functions, from mitosis to locomotion. The functional rigidity of a cell is usually thought to result from three interpenetrating networks of filamentous biopolymers: actin microfilaments, microtubules, and intermediate filaments (IF). The mechanical properties of both filamentous actin (F-actin) and microtubule networks have been extensively studied, both directly in cells and in model in vitro systems, consisting of reconstituted networks of purified proteins. The assembly and structures of actin and tubulin polymers, coupled to ATP and GTP hydrolysis, respectively, give rise to fascinating dynamics that have attracted experimentalists, theorists, and modelers for decades, trying to understand their properties and functions. In addition, the diverse molecular motors that run along these tracks are central to much of cell dynamics and vesicle transport. By contrast, intermediate filaments do not hydrolyze nucleotides, do not exhibit structural polarity, and have no motors that run along them. Also, unlike actin and tubulin, which exist in very similar forms in nearly all eukaryotic cells, IF proteins appeared later in evolution and mutated rapidly to form distinct molecular species in different cell types. Some classes of IFs can be genetically ablated in mice without the mice necessarily losing viability and resulting in some cases in a barely discernable phenotype. However, the IFs expressed in epithelial cells, keratin IFs (or KIFs), are required for normal epithelial function, and mutations in these proteins can cause devastating human diseases. In an article in a recent issue of PNAS, Sivaramakrishnan et al. reported on the results of a remarkable study of the micromechanical properties of IF networks that should begin to redress our imbalance in understanding of the mechanics of the different biopolymer networks. These authors show that the KIF networks are essential for the mechanical integrity of the cell, and without them, cells such as alveolar epithelial cells would be helpless to withstand the forces they experience as the lung inflates and stretches them.

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