Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a calcium-dependent nuclear softening driven by loss of H3K9me3-marked heterochromatin. The resulting changes in chromatin rheology and architecture are required to insulate genetic material from mechanical force. Failure to mount this nuclear mechanoresponse results in DNA damage. Persistent, high-amplitude stretch induces supracellular alignment of tissue to redistribute mechanical energy before it reaches the nucleus. This tissue-scale mechanoadaptation functions through a separate pathway mediated by cell-cell contacts and allows cells/tissues to switch off nuclear mechanotransduction to restore initial chromatin state. Our work identifies an unconventional role of chromatin in altering its own mechanical state to maintain genome integrity in response to deformation.

Microfluorescence methods were used to examine monolayer-monolayer and bilayer-substrate coupling in bilayers deposited on glass substrates. In the first part, lateral diffusion of lipid probes in individual lipid layers was measured by the fluorescence recovery after photobleach technique. The aim was to evaluate viscous molecular friction (i) between monolayers that form a single bilayer and (ii) between a bilayer and an adjacent substrate based on a recent phenomenological theory for particle mobility in substrate-coupled membranes (Evans and Sackmann, J. Fluid Mech. 194 (1988) 553 [1]). To obtain coefficients for friction between monolayers, a bilayer was formed with the first (proximal) monolayer fixed to the glass substrate by Si-O-bonds (using silanes) or by ion bridges (using cadmium arachidate) ; then, probe diffusion was measured in the second (distal) monolayer formed by phospholipids. The coefficient for viscous friction (defined by b s-interfacial shear stress/interfacial « slip » velocity) between monolayers with fluid chains (DMPC or DOPC on silane) was calculated to be in the range bs = 106-107 dyn-sec/cm3 ; between a fluid and a solid monolayer (DOPC on Cd-arachidate), the frictional coefficient was much larger, i.e. bs = 1-5 × 108 dyn-sec/cm3. For two opposing monolayers with liquid chains, it was found that bs increased with the degree of interdigitation between the hydrocarbon chains. To investigate the effect of lubrication by a water film between a fluid bilayer and the substrate, the substrate was first Argon sputtered which acted to separate the proximal monolayer from the substrate by a thin lubricating water film (thickness in nm region). The frictional coefficient between the bilayer and the substrate was measured to be in the range bs = 2 x 103-3 × 105 dyn-sec/cm3 which implied that the film thickness was from 1-50 nm. In the second part, we studied the effect of monolayer-monolayer and bilayer-substrate coupling on the acyl-chain crystallization transitions in monolayers of supported bilayers. Symmetric bilayers (separated from the substrate by a water film) exhibited sharp phase transitions at about the same transition temperature as the free bilayers. The transition temperature for asymmetric bilayers was between the transition temperatures for the individual monolayer components. Bilayers formed by phospholipid monolayers on silanes showed a concerted but continuous phase transition which appeared to be due to the constraint of fixed total area and interdigitation of the two monoalayers. By doping the monolayers with different fluorescent probes (NBD and Texas Red lipid analogs), it was demonstrated that, when the proximal layer was in a solid or liquid-solid coexistence state, a phase transition was induced in the superficial monolayer even if this layer was deposited from the fluid state. It was also observed that the patterns of fluid and solid domains in both layers were in complete register. On the other hand, a fluid monolayer of unsaturated lipids on tightly -packed crystalline proximal monolayer was able to undergo a separate phase transition