CNIC: U.S.-Netherlands Project Development of Experimental and Theoretical Tools to Investigate the Non-equilibrium Mechanics of the Cell Nucleus

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

This U.S.-Netherlands project development visit will catalyze new collaboration between the PI's experimental group at the University of Massachusetts, Amherst, and the theoretical group of Prof. Fred MacKintosh at the VU University, in Amsterdam. Working with the PI's data from experiments on chromosomal/spindle motion during cell division, new theoretical models will be developed jointly to interpret her data and extend UV University's active network models. The goal of the new collaboration is to ceate a bridge going from theoretical models to results with biological implications for advancing our basic understanding of how chromosomes move during cell division. With preliminary results, the partners expect to establish a theoretical and quantitative framework to characterize and help explain the mechanics of the microenvironment of the living cell nucleus. Involvement of one U.S. graduate student in this activity will provide valuable early career research experience with both experimental and theoretical approaches, as well as exposure to a range of biophysical systems and methods, including advanced microscopy. If successful, findings should contribute to our ability to address the challenges currently posed by quantitative intracellular microrheology and prepare a foundation for the U.S.-Netherlands team's longer term research. Growth in organisms, from embryo to old age, proceeds from cell division. It is a fundamental part of the biology of organisms and obtaining an appropriate model for the motion of chromosomes during the process could help with understanding of this basic event. During research visits to Amsterdam, U.S. experimental results on the nonequilibrium motions of fluorescent probes (in the cell nucleus and in an in vitro minimal model for activity in the nuclear mechanical environment) will be analyzed theoretically. Cooperative efforts will focus on the frequency dependence of the fluctuation enhancement and the dependence on the size scale of the probes, attached to a chromosome locus or spanning the entire spindle. These experiments and theory on the dynamic behavior of condensed DNA in living cells and in vitro could lead to a new way of thinking about the vital motion in living cells and about its role in the way DNA behaves in the nucleus.