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Here, we demonstrate that T cell spreading is accompanied by nuclear deformation and increased chromatin compaction. Reducing chromatin compaction, which is known to soften the nucleus, enhances cell spread area and nuclear deformation but decreases F-actin accumulation and peripheral enrichment at the immune synapse. Conversely, enhancing chromatin compaction restricts spreading and deformation but promotes peripheral F-actin organization. This reveals a reciprocal relationship between chromatin compaction and cytoskeletal organization. We identify SUN proteins and myosin as key mediators through which chromatin compaction modulates actin morphology and cell shape, enabling T cells to adapt to antigen-presenting surfaces of varying stiffness. These findings underscore the pivotal role of chromatin compaction in T cell activation, highlighting the mechanical interplay between the nucleus and cytoskeleton, and suggesting novel insights into T cell mechano-responsiveness.<\/jats:p>","DOI":"10.1091\/mbc.e25-10-0487","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:39:19Z","timestamp":1783539559000},"source":"Crossref","is-referenced-by-count":1,"title":["Nuclear morphology and chromatin compaction modulate T cell cytoskeletal remodeling and immune synapse formation"],"prefix":"10.1091","volume":"37","author":[{"given":"Ivan","family":"Rey-Suarez","sequence":"first","affiliation":[{"name":"Bio-imaging Resource Center, The Rockefeller University, New York, NY 10065, USA"},{"name":"Institute for Physical Science and Technology, University of Maryland, College Park, MD 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