A novel nanotopography-based approach for reshaping nuclear morphology and gene transcription

The cell nucleus acts as a control center for the cell, playing a vital role in how cells respond to physical forces from their environment. However, our understanding of these responses remains incomplete due to a lack of proper tools for manipulating cells and their nuclei. To tackle this challenge, we are developing advanced nanostructured surfaces. Placing cells onto these surfaces allows us to deform the cell nucleus and explore how specific genes react to controlled mechanical inputs. Recent progress in nanofabrication, experimental techniques, and computational tools has made this innovative approach possible. This research is significant because it could lead to improved treatments for diseases like cancer, where altered mechanical responses in cells are a critical factor.

The cell and its nucleus constantly responds and adapts to external mechanical cues. Alterations in nuclear morphology as well as in the state of DNA condensation impact cell homeostasis, differentiation and pathogenesis. Indeed, alterations in nuclear morphologies have been considered a hallmark of cancer for decades. However, tools for inducing controlled nuclear deformations and for measuring cell and nuclear response are lacking. This severely hampers our ability to properly understand and predict how cells respond to mechanical changes in their surroundings. In this project, we propose the development and implementation of novel nanostructured surfaces to induce controlled nuclear deformation, and subsequently read out nuclear effects on DNA condensation and gene expression. This is now becoming possible due to recent progress in nanofabrication coupled with cutting edge experimental and computational tools developed by us and others.