APS March Meeting 2020
Volume 65, Number 1
Monday–Friday, March 2–6, 2020;
Denver, Colorado
Session X19: Frontiers in Actomyosin Stress Sensing and the Dynamics of the Cytoskeleton
11:15 AM–2:15 PM,
Friday, March 6, 2020
Room: 207
Sponsoring
Unit:
DBIO
Chair: John Crocker, University of Pennsylvania
Abstract: X19.00004 : How immune cells respond to physical cues – the role of cytoskeletal dynamics*
Abstract
Presenter:
Arpita Upadhyaya
(University of Maryland, College Park)
Author:
Arpita Upadhyaya
(University of Maryland, College Park)
The activation of lymphocytes, an essential step in the adaptive immune response, involves the binding of specialized receptors with antigens. This results in large-scale dynamics and re-structuring of the cytoskeleton, and movement of receptors into sub-micron clusters, which are critical for immune cell activation. Antigen presenting surfaces possess a wide variety of physical attributes, which influence cytoskeletal organization and receptor mobility, but how cells respond to these physical cues is not well understood. I will summarize our recent studies that examine how immune cells respond to physical cues such as surface mobility and topography. Regulation of membrane receptor mobility is important in tuning cellular response to external signals, such as during B cell signaling following the binding of B cell receptors (BCR) to antigen. We have used single molecule imaging to examine BCR movement and machine learning techniques to relate receptor trajectories to their signaling states. We find that the dynamic actin network fine-tunes receptor mobility and receptor-ligand interactions, thereby modulating B cell signaling. In vivo, B cells encounter surfaces of antigen presenting cells that are highly convoluted with a wide range of curvatures. We have used nanotopographic surfaces that allow systematic variation of geometric parameters to show that surface features on a subcellular scale influence B cell signaling and actin dynamics. Nanotopography-induced actin dynamics requires BCR signaling, actin polymerization, and myosin contractility. The topography of the stimulatory surface also modulates the distribution of BCR clusters and calcium signaling in activated B cells. Active cytoskeletal control of receptor diffusion may be a general feature that directs how diverse cell types respond to physical stimuli and transduce external signals into internal chemical signals.
*This work was funded by the grants NIH AI122205, NSF PHY 1607645 and NSF PHY 1806903.