Power-law rheology of isolated nuclei with deformation mapping of nuclear sub-structures

¹ University of Pennsylvania

^* To whom correspondence should be addressed. E-mail: discher{at}seas.upenn.edu.

Submitted on March 9, 2005
Revised on April 14, 2005
Accepted on 19 July 2005

	Abstract

Force-induced changes in genome expression as well as remodeling of nuclear architecture in development and disease motivate a deeper understanding of nuclear mechanics. Chromatin and GFP-lamin B dynamics were visualized in micropipette aspiration of isolated nuclei, and both were shown to contribute to viscoelastic properties of the somatic cell nucleus. Reversible swelling by almost 200% in volume, with changes in salt, demonstrates the resilience and large dilational capacity of the nuclear envelope, nucleoli, and chromatin. Swelling also proves an effective way to separate the mechanical contributions of nuclear elements. In unswollen nuclei, chromatin is a primary force-bearing element, whereas swollen nuclei are an order of magnitude softer with the lamina sustaining much of the load. In both cases, nuclear deformability increases with time, scaling as a power-law - thus lacking any characteristic timescale - when nuclei are either aspirated or indented by atomic force microscopy. The nucleus is stiff and resists distortion at short times, but it softens and deforms more readily at longer times. Such results indicate an essentially infinite spectrum of time scales for structural reorganization, with implications for regulating genome expression kinetics.

Key Words: Cellular mechanics, cellular rheology, chromatin organization, micropipette aspiration, nuclear envelope, nuclear structure

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