Nuclear mechano-confinement induces geometry-dependent HP1α condensate alterations

Cells sense external physical cues through complex processes involving signaling pathways, cytoskeletal dynamics, and transcriptional regulation to coordinate a cellular response. A key emerging principle underlying such mechanoresponses is the interplay between nuclear morphology, chromatin organization, and the dynamic behavior of nuclear bodies such as HP1α condensates. Here, applying super-resolution live cell imaging, we report a hitherto undescribed level of mechanoresponse triggered by cell confinement below their resting nuclear diameter, which elicits changes in the number, size and dynamics of HP1α nuclear condensates. Utilizing biophysical polymer models, we find that HP1α condensates become radially redistributed in the nucleus, dependent on the combined effect of HP1α's crosslinking activity and nuclear flattening. These insights shed new light on the complex relationship between external forces and changes in nuclear shape and chromatin organization in cell mechanoreception.