TY - JOUR
T1 - Spatial-temporal dynamics of collective chemosensing
AU - Sun, Bo
AU - Lembong, Josephine
AU - Normand, Valery
AU - Rogers, Matthew
AU - Stone, Howard A.
PY - 2012/5/15
Y1 - 2012/5/15
N2 - Although the process of chemosensing by individual cells is intrisically stochastic, multicellular organisms exhibit highly regulated responses to external stimulations. Two key elements to understand the deterministic features of chemosensing are intercellular communications and the role of pacemaker cells. To characterize the collective behavior induced by these two factors, we study the spatial-temporal calcium dynamics of fibroblast cells in response to ATP stimulation. We find that closely packed cell colonies exhibit faster, more synchronized, and highly correlated responses compared to isolated cells. In addition, we demonstrate for chemosensing the existence of pacemaker cells and how the presence of gap junctions impact the first step of the collective response. By further comparing these results with the calcium dynamics of cells embedded in thin hydrogel films, where intercellular communication is only possible via diffusing molecules, we conclude that gap junctions are required for synchronized and highly correlated responses among cells in high density colonies. In addition, in high density cell colonies, both communication channels lead to calcium oscillations following the stimulation by external ATP. While the calcium oscillations associated with cells directly exposed to external flows were transient, the oscillations of hydrogel trapped cells can persist with a fundamental frequency and higher harmonics. Our observations and measurements highlight the crucial role of intercellular signaling for generating regulated spatial and temporal dynamics in cell colonies and tissues.
AB - Although the process of chemosensing by individual cells is intrisically stochastic, multicellular organisms exhibit highly regulated responses to external stimulations. Two key elements to understand the deterministic features of chemosensing are intercellular communications and the role of pacemaker cells. To characterize the collective behavior induced by these two factors, we study the spatial-temporal calcium dynamics of fibroblast cells in response to ATP stimulation. We find that closely packed cell colonies exhibit faster, more synchronized, and highly correlated responses compared to isolated cells. In addition, we demonstrate for chemosensing the existence of pacemaker cells and how the presence of gap junctions impact the first step of the collective response. By further comparing these results with the calcium dynamics of cells embedded in thin hydrogel films, where intercellular communication is only possible via diffusing molecules, we conclude that gap junctions are required for synchronized and highly correlated responses among cells in high density colonies. In addition, in high density cell colonies, both communication channels lead to calcium oscillations following the stimulation by external ATP. While the calcium oscillations associated with cells directly exposed to external flows were transient, the oscillations of hydrogel trapped cells can persist with a fundamental frequency and higher harmonics. Our observations and measurements highlight the crucial role of intercellular signaling for generating regulated spatial and temporal dynamics in cell colonies and tissues.
KW - Cell signaling
KW - Emergent behavior
UR - http://www.scopus.com/inward/record.url?scp=84861211048&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861211048&partnerID=8YFLogxK
U2 - 10.1073/pnas.1121338109
DO - 10.1073/pnas.1121338109
M3 - Article
C2 - 22566661
AN - SCOPUS:84861211048
SN - 0027-8424
VL - 109
SP - 7753
EP - 7758
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
ER -