Nuclear mechanobiology – from striated muscle disease to ultrarapid cellular mechanosensing

The nucleus is the defining feature of eukaryotic cells. While most research has focused on the genomic information contained within the nucleus, recent findings highlight the importance of its mechanical properties and responses to applied forces in determining cellular functions and processes. Using a comprehensive and multidisciplinary research approach that combines the development of novel experimental assays to measure subcellular mechanics in vitro and in vivo with cell and molecular biology techniques and in vivo models, the Lammerding laboratory has made several seminal contributions to the emerging field of 'nuclear mechanobiology'. This talk will showcase recent discoveries, including (1) how nuclear deformability enables cells to navigate through confined spaces and the resulting impact on nuclear integrity, chromatin organization, and gene expression; (2) applying insights from nuclear mechanobiology to develop novel treatments for muscular dystrophy and dilated cardiomyopathy caused by mutations in nuclear envelope proteins, such as lamins A/C; and (3) utilizing advanced genomics techniques like precision nuclear run-on sequencing (PRO-seq) to investigate how cells rapidly convert mechanical stimuli into changes in gene expression, revealing the nucleus's role in regulating mechanoresponsive genes. Join us for a presentation featuring captivating videos of cells squeezing through tight spaces and learn more about the fascinating world of nuclear mechanobiology.