Modeling the self-organization property of keratin intermediate filaments

Jin Seob Kim, Chang Hun Lee, Pierre A. Coulombe

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2748-2756
Number of pages9
JournalBiophysical Journal
Volume99
Issue number9
DOIs
StatePublished - Nov 3 2010

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Intermediate Filaments
Keratins
Keratin-14
Keratin-5
Keratinocytes
Epidermis
Epithelium
Epithelial Cells

ASJC Scopus subject areas

  • Biophysics

Cite this

Modeling the self-organization property of keratin intermediate filaments. / Kim, Jin Seob; Lee, Chang Hun; Coulombe, Pierre A.

In: Biophysical Journal, Vol. 99, No. 9, 03.11.2010, p. 2748-2756.

Research output: Contribution to journalArticle

Kim, Jin Seob ; Lee, Chang Hun ; Coulombe, Pierre A. / Modeling the self-organization property of keratin intermediate filaments. In: Biophysical Journal. 2010 ; Vol. 99, No. 9. pp. 2748-2756.
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