MechE Colloquium: How do forces transmitted from a cell's environment affect DNA organization?


Event details

Date 21.03.2023
Hour 12:0013:00
Speaker Prof. Vivek Shenoy, Center for Engineering Mechanobiology and School of Engineering and Applied Sciences, University of Pennsylvania
Location Online
Category Conferences - Seminars
Event Language English
Abstract: Microscale changes in tissue environment are translated to changes in cell behavior and phenotype, yet the mechanisms behind how these phenotypic changes occur are poorly understood. Here, we describe and model chromatin, which stores genetic information within the cell nucleus, as a dynamic nanomaterial whose configuration is modulated by chemo-mechanical cues in the microenvironment [1,2]. Our findings indicate that physiologic chemo-mechanical cues can directly regulate chromatin architecture in progenitor cell populations. Through direct experimental observation and modeling that incorporates phase transitions and histone methylation kinetics, we demonstrate that soft environmental cues drive chromatin relocalization to the nuclear boundary (leading to the formation of Lamin-Associated Domains) and compaction. Conversely, dynamic stiffening attenuates these changes. We show how methylation and acetylation impact the spatial distribution of the stiffness of the nucleus. Interestingly, in diseased human fibrous tissue cells, this link between mechanical inputs and chromatin nano-scale remodeling is abrogated. These data indicate that chromatin dynamics and plasticity may be hallmarks of disease progression and targets for therapeutic intervention.

[1] Heo et al., Diseased Fibrous Tissue Cells Lose Capacity for Dynamic Nanoscale Genome Reorganization in Response to Changing Chemo-Mechanical Cues, NATURE BIOMEDICAL ENGINEERING AUGUST 2022.
[2] F. Alisafaei et al., Regulation of Nuclear Architecture, Mechanics and Nucleo-cytoplasmic Shuttling of Epigenetic Factors by Cell Geometric Constraints PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, 116(27): 13200-13209, JULY 2019.

Biography: Vivek Shenoy is the Eduardo D. Glandt President’s Distinguished Professor in the School of Engineering and Applied Sciences at the University of Pennsylvania. Dr. Shenoy's research focuses on developing theoretical concepts and numerical methods to understand the basic principles that control the behavior of biological systems. He has used rigorous analytical methods and multiscale modeling techniques, ranging from molecular to continuum methods, to gain physical insight into a myriad of problems in mechanobiology and biomaterials. He is the principal investigator and director of the NSF-funded Science and Technology Center for Engineering Mechanobiology established in 2016 and an MPI of the National Cancer Institute-funded Metastasis Research Network (MetNet) center funded in 2021. Shenoy is an ISI Web of Science/Clarivate Analytics Highly Cited Researcher.

Practical information

  • General public
  • Free



MechE Colloquium: How do forces transmitted from a cell's environment affect DNA organization?