Regulation of nuclear deformation via spatiotemporal modulation of cytoskeleton forces on photo-switchable surfaces

Nuclear deformations are known to influence the 3D organization of chromatin, ultimately regulating cell fate decisions through gene transcription activity. Understanding and controlling this relationship offers valuable insights into fundamental cellular processes and potential strategies for cell engineering. While this phenomenon is well known, direct evidence of how dynamic external physical cues regulate chromatin structure has remained elusive. This study presents a method to dynamically regulate chromatin architecture using photo-switchable pDR1m-based mechano-modulating surfaces. Through in-situ photo-patterning and erasure of surface nanogratings, we achieved spatiotemporal regulation of the intensity and distribution of cytoskeletal forces transmitted to the nuclear envelope and reversible nuclear deformations in MCF10A cells. These nanotopography induced cytoskeletal forces facilitated the modulation of chromatin compaction and spatial reorganization of heterochromatin domains. Therefore, our findings establish a dynamic, reversible platform to manipulate chromatin organization and control cell activity, elucidating the dynamic interplay between the cytoskeleton, nucleus, and chromatin as mediated by cell-material interactions.