NSF-ANR MCB/PHY Building Quantitative Models of Eukaryotic Cell Motility

Cell motility through tissues is a key aspect of both healthy developmental processes and the spread of cancer to metastatic sites. Hence, understanding the key ingredients behind this process in a quantitatively predictive manner is of tremendous interest both for fundamental biophysics and practical applications. This award focuses on a joint experiment-theory project to further this understanding.

The methodology will rely on constructing a detailed computational model taking into account features of the motility process that have heretofore not been included in any such approach. These features include how the cell utilizes “blebbing” (pressure induced protrusions of the cell membrane) to move forward and how it deforms its nucleus to allow passage through tight spaces.

These aspects will be investigated experimentally by studying cells moving through carefully designed microstructures and measuring their morphology and mechanics during the motility process; these experiments, carried out by French collaborators from the Ecole Normale in Paris, will provide critical data for both developing and testing the computational model. Coupled to the research aspects of this award will be the training of students to address highly interdisciplinary research areas and also the furthering of scientific exchanges between teams in the US and France, who have historically approached this subject using complementary perspectives.

In this award the investigators propose to develop a new generation of phase-field-based models for studying eukaryotic cell motility, especially when it takes place in complex geometries. Previous efforts have neglected important features such as cortex contractility, the role of the nucleus, and the ability of cells to switch motility phenotypes. Now, recent advances in both available experimental information and computational techniques coupled with raw computational power will enable this critical advance to tackle a fundamental aspect of cell physiology.

The creation of such a new generation model will yield results that have wide implications for both developmental processes and disease states such as metastatic cancer. This project brings together principal investigators who have extensive experience in the nonlinear dynamics underlying cytoskeletal dynamics and cell motility (Levine), and in the development of advanced analytic and computational techniques that have transformed the phase-field idea into a powerful and quantitatively accurate tool for free surface problems in non-living systems (Karma).

The proposal also will also involve collaborators from the Ecole Normale who will design and conduct specific experiments to provide needed data to further model development and validation.

This collaborative US/France project is supported by the Physics of Living Systems program in the Division of Physics at the US National Science Foundation and the French Agence Nationale de la Recherche, where NSF funds the US investigator and ANR funds the partners in France.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.