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• W1997092340 abstract "Keratin intermediate filaments (IFs) fulfill an important function of structural support in epithelial cells. The necessary mechanical attributes require that IFs be organized into a crosslinked network and accordingly, keratin IFs are typically organized into large bundles in surface epithelia. For IFs comprised of keratins 5 and 14 (K5, K14), found in basal keratinocytes of epidermis, bundling can be self-driven through interactions between K14's carboxy-terminal tail domain and two regions in the central α-helical rod domain of K5. Here, we exploit theoretical principles and computational modeling to investigate how such cis-acting determinants best promote IF crosslinking. We develop a simple model where keratin IFs are treated as rigid rods to apply Brownian dynamics simulation. Our findings suggest that long-range interactions between IFs are required to initiate the formation of bundlelike configurations, while tail domain-mediated binding events act to stabilize them. Our model explains the differences observed in the mechanical properties of wild-type versus disease-causing, defective IF networks. This effort extends the notion that the structural support function of keratin IFs necessitates a combination of intrinsic and extrinsic determinants, and makes specific predictions about the mechanisms involved in the formation of crosslinked keratin networks in vivo." @default.
• W1997092340 created "2016-06-24" @default.
• W1997092340 creator A5015341073 @default.
• W1997092340 creator A5074920093 @default.
• W1997092340 creator A5087132038 @default.
• W1997092340 date "2010-11-01" @default.
• W1997092340 modified "2023-09-29" @default.
• W1997092340 title "Modeling the Self-Organization Property of Keratin Intermediate Filaments" @default.
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• W1997092340 doi "https://doi.org/10.1016/j.bpj.2010.09.023" @default.
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