High stretchability, strength, and toughness of living cells enabled by hyperelastic vimentin intermediate filaments
Jiliang HuYiwei LiYukun HaoTianqi ZhengSatish Kumar GuptaGerman Alberto ParadaHuayin WuShaoting LinShida WangXuanhe ZhaoRobert D. GoldmanShengqiang CaiMing Guo
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Abstract:
Significance Intermediate filaments (IFs) remain the least understood with respect to their functions in mammalian cells even though they have been related to many devastating human diseases. Here we use optical tweezers to perform micromechanical measurements in living cells and in IF enriched cytoskeletons devoid of actin and microtubules. We identify that cytoskeletal vimentin IFs (VIFs) provide cells with a hyperelastic rubber-like network that regulates the essential mechanical properties of mammalian cells including stretchability, strength, resilience, and toughness. We show that VIFs maintain cell integrity and viability under conditions involving extreme deformations. We further show that the stretchy VIF network can effectively disperse locally induced mechanical stress to larger regions within individual cells, enabling the dissipation of energy throughout a cell.Keywords:
Hyperelastic material
Resilience
The proposed function of intermediate filaments is to provide a cell type-specific structural framework that maintains cell shape and organelle distribution and mediates signal transduction through its connections with the plasma membrane and the nucleus. Vimentin is the intermediate filament protein expressed in B lymphocytes. Immunocytochemical analysis of the high salt-stable cytoskeletons from B cells stimulated with anti-Ig revealed an increased accumulation of vimentin in the cytoskeleton compared to nontreated controls. This increased accumulation of vimentin in the cytoskeleton was manifested by the organization of vimentin into extensive filamentous arrays (EFA) as viewed in the fluorescent microscope. In contrast to the effects of anti-Ig, activation of B cells with LPS did not induce the organization of vimentin into EFA. This suggested that signals unique to anti-Ig directed EFA formation. Immunocytochemical results were verified by biochemical analysis showing that vimentin was more abundant in isolated cytoskeletons from anti-Ig activated B cells, than cytoskeletons isolated from LPS-activated B cells. These observations established a relationship between increased content of vimentin in the cytoskeleton and the formation of EFA. By testing a wide variety of activating agents, we were able to correlate increased vimentin expression in the cytoskeleton to activating agents that cross-link membrane Ig. It appeared that treatment of B cells with LPS prohibited the induction of EFA by anti-Ig because cotreatment with both anti-Ig and LPS resulted in decreased vimentin accumulation in the cytoskeleton to a level less than that in resting cells. The significance of these results with regard to B cell biology is discussed.
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IFAPa-400, a 400-kDa developmentally regulated protein thought to be associated with intermediate filaments, has been purified from chick embryo hearts to investigate its interaction with vimentin and other IF proteins and to identify other cellular components to which this cytoskeletal protein associates. Previous studies suggested that this protein was associated with the vimentin-containing intermediate filament lattice of myoblasts and neuroblasts before their terminal differentiation, providing these cells with a particular intermediate filament cytoskeleton that could satisfy specific mechanical requirements during their intense morphogenetic activities. Although IFAPa-400 partially reassociated with vimentin and desmin in disassembly–reassembly experiments using crude IF preparations from chick embryo hearts, in vitro recombination of purified IFAPa-400 with vimentin and desmin failed to demonstrate any direct association. When purified IFAPa-400 was used as a probe in blot overlay assays, however, specific binding to vimentin and desmin was observed, providing the first evidence of a physical association between IFAPa-400 and intermediate filament proteins. The blot overlay experiments also demonstrated that IFAPa-400 binds to two unidentified polypeptides of 19 and 32 kDa. These results are thus consistent with the hypothesis that a structural lattice requiring a vimentin–IFAPa-400 combination constitutes the intermediate filament system of myogenic and neurogenic cells.Key words: cytoskeleton, intermediate filaments, intermediate filament associated proteins, vimentin, IFAPa-400.
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The stable coexistence of the intermediate filament proteins desmin and vimentin in vascular smooth muscle cells raises questions about the relative amounts of the two proteins in different individual cells, and the distribution of the two proteins in individual intermediate filaments within each cell. These questions have been explored by double immunofluorescence microscopy and double immunoelectron microscopy on semi-thin and ultrathin frozen sections of chicken aorta. The former studies indicate that there is a surprisingly wide variation in the desmin/vimentin ratio in adjacent smooth muscle cells. The latter studies show that both proteins are present in individual intermediate filaments, in clustered arrays rather than uniformly distributed. These findings extend earlier related results, and suggest that the turnover of intermediate filaments may involve the remodelling of existing filaments rather than their de novo polymerization.
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Human endothelial cells prepared from unbilical cords are characterized in parallel by electron microscopy and indirect immunofluorescence microscopy using specific antibodies against different classes of intermediate-sized filaments. The strongly developed, loose bundles of intermediate-sized filaments typically found in these cells are not decorated by antibodies against prekeratin or antibodies against smooth muscle desmin. They are, however, strongly decorated by antibodies directed against murine "vimentin," i.e., the 57,000 mol wt polypeptide which is the major protein of the intermediate-sized filaments predominant in various cells of mesenchymal origin. Cytoskeletal preparations greatly enriched in intermediate-sized filaments show the enrichment of a polypeptide band comigrating with murine vimentin. This shows that the intermediate-sized filaments that are abundant in human endothelial cells are predominantly of the vimentin type and can be demonstrated by their cross-reaction with the vimentin of rodents. These data also strengthen the evidence for several subclasses of intermediate-sized filaments, which can be distinguished by immunological procedures.
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