Analyzing the Motion of Immune Cell Surface Molecules

Associated People:

Daniel Coombs (University of British Columbia)

Raibatak Das (University of British Columbia)

Christopher W. Cairo (Univesity of Alberta)

Quentin J. Baca (Harvard University)

Deepti Pradhan (Yale University)

Jon S. Morrow (Yale University)

Amgad Albohy (University of Alberta)

David E. Golan (Harvard University)

Associated Sites:
PIMS University of British Columbia
Associated PIMS Programs:

IGTC in Mathematical Biology

Many important biological processes begin when a target molecule binds to a cell surface receptor protein. This event leads to a series of biochemical reactions involving the receptor and signalling molecules, and ultimately a cellular response. Surface receptors are mobile on the cell surface and their mobility is influenced by their interaction with intracellular proteins. We wanted to understand the details of these interactions and how they are affected by cellular activation. This led us to an particular experimental technique called single particle tracking (SPT), which uses optical microscopy to study the motion of cell-surface receptors. We proposed rigorous methods for the analysis of SPT data that can identify reduced receptor mobility as a result of transient binding to intracellular proteins. Using our analysis we were able to reliably differentiate receptor motion when a receptor is freely diffusing on the membrane versus when it is interacting with an intracellular protein. By observing the frequency of transitions between free and bound states, we were able to estimate reaction rates for the interaction. This method has now been applied to several surface receptors on T cells of the immune system, leading us to generate novel biological hypotheses about the interactions between the receptors and the intracellular milieu, in each case.