ERI: Competition in Cell Collisions: Towards Engineerable Living Interfaces

This Engineering Research Initiation (ERI) award funds research that will investigate the principles governing the interactions at the interface between different groups of cells. These interfaces are crucial in biological processes such as tissue development, wound healing, and cancer metastasis. The project aims to understand how cells from different tissues interact and organize themselves when they come into contact. This research is significant because it attempts to addresses fundamental questions about cell behavior and organization, which are essential for advancing our knowledge of biology and medicine. This work supports the progress of science and advances national health by providing a deeper understanding of the physical and biological mechanisms that drive cell interactions. By understanding these interactions, the project could lead to new ways to control tissue repair and healing, prevent cancer spread, and design engineered tissues. The work will also involve transformation of an online resource, the Cell Migration Seminars Series, into an open tool for learning.

Confluent collectives of epithelial cells line every organ surface and body cavity. While the homeostatic epithelial collective remains solid-like and sedentary, previously stationary epithelial collectives mobilize and undergo large-scale, coordinated motion during development, wound healing, and cancer metastasis. This collective fluidization necessarily leads to the creation and maintenance of interfaces between tissues with distinct physical and biological identities. However, the biological and physical rules governing the spatial and temporal evolution of these active interfaces are largely unknown. While the role of gene expression patterns and specific signaling pathways has provided significant understanding of the formation, sharpening, and maintenance of tissue boundaries during developmental processes, significantly less is understood about rules governing the interactions of different cell types as might occur after injury or during cancer metastasis. Both biological and physical mechanisms have been suggested to govern boundary dynamics after collisions of distinct cell types, but understanding remains limited. Here, the fundamental mechanobiology of heterotypic tissue interface dynamics will be investigated through variation of physical and biological properties of the constituent cellular collectives. Preliminary data indicates that collective behaviors following collisions are complex, emergent, and unexpected. Antagonistic migration assays will be used to create a reproducible tissue interface between any two cell types. The resultant tissue interface dynamics will be determined, and underlying cell-substrate tractions and cell-cell stresses governing the emergent behaviors at the interface will be measured. These studies intend to advance predictive understanding of collective cellular behaviors towards the ability to design a cellular interface with programmable morphodynamics.

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.

Award Number: 2502201
Principal Investigator: Jennifer Mitchel
Funds Obligated: $199,982
State: CT