Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Wednesday Speaker Abstracts

Self-healing of Holes in the Nuclear Envelope Dan Deviri 1 , Dennis Discher 2 , Samuel Safran 1 . 1 Weizmann Institute of Science, Rehovot, Israel, 2 University of Pennsylvania, Philadelphia, PA, USA. During migration of cells in vivo, both in pathological processes such as cancer metastasis [1] or physiological events such as immune cells migration through tissue [2], the cells must move through narrow interstitial spaces which can be smaller than the nucleus. This can induce extensive deformation of the nucleus which, according to recent experiments, results in hole formation in the nuclear envelope that can lead to cell death [3] if not prevented or healed within an appropriate time. The nuclear envelope, which can be modeled as a thin, viscoelastic gel whose elasticity and viscosity primarily depend on the lamin composition [4] may utilize self- healing mechanisms that allow the hole to be sealed after the stresses that created it are removed. Here, we present a viscoelastic model of the nuclear envelope and quantify the conditions under which the self-healing of existing holes can be related to the viscoelastic properties and to the ratio of lamin A/C and B in the nuclear envelope. Disease states in which the lamin compositions are flawed can result in nuclear envelope holes that do not self-repair, leading to the expulsion of chromatin to the cytoplasm. [1] C. M. Denais et al. Nuclear envelope rupture and repair during cancer cell migration. Science, in press, 2016. [2] M. Raab, et al. Escrt iii repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death. Science, in press, 2016. [3] T. Harada, et al. Nuclear lamin stiffnessis a barrier to 3d migration, but softness can limit survival. The Journal of Cell Biology, 204(5):669-682,2014. [4] J. Swift, et al. Nuclear lamin-a scales with tissue stiffness and enhances matrix-directed differentiation. Science, 341(6149):1240104, 2013.

Imaging How Cells Choose Their Fate, Shape and Position in the Mouse Embryo Nicolas Plachta Institute of Molecular & Cell Biology, Agency for Science, Technology & Research (A*STAR), Singapore No Abstract

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