TY - JOUR

T1 - Cell surface topology creates high Ca2+ signalling microdomains

AU - Brasen, Jens Christian

AU - Olsen, Lars Folke

AU - Hallett, Maurice B

N1 - 2010 Elsevier Ltd. All rights reserved.

PY - 2010/4

Y1 - 2010/4

N2 - It has long been speculated that cellular microdomains are important for many cellular processes, especially those involving Ca2+ signalling. Measurements of cytosolic Ca2+ report maximum concentrations of less than few micromolar, yet several cytosolic enzymes require concentrations of more than 20 microM Ca2+ to be activated. In this paper, we have resolved this apparent paradox by showing that the surface topology of cells represents an important and hitherto unrecognized feature for generating microdomains of high Ca2+ in cells. We show that whereas the standard modeling assumption of a smooth cell surface predicts only moderate localized effects, the more realistic "wrinkled" surface topology predicts that Ca2+ concentrations up to 80 microM can persist within the folds of membranes for significant times. This intra-wrinkle location may account for 5% of the total cell volume. Using different geometries of wrinkles, our simulations show that high Ca2+ microdomains will be generated most effectively by long narrow membrane wrinkles of similar dimensions to those found experimentally. This is a new concept which has not previously been considered, but which has ramifications as the intra-wrinkle location is also a strategic location at which Ca2+ acts as a regulator of the cortical cytoskeleton and plasma membrane expansion.

AB - It has long been speculated that cellular microdomains are important for many cellular processes, especially those involving Ca2+ signalling. Measurements of cytosolic Ca2+ report maximum concentrations of less than few micromolar, yet several cytosolic enzymes require concentrations of more than 20 microM Ca2+ to be activated. In this paper, we have resolved this apparent paradox by showing that the surface topology of cells represents an important and hitherto unrecognized feature for generating microdomains of high Ca2+ in cells. We show that whereas the standard modeling assumption of a smooth cell surface predicts only moderate localized effects, the more realistic "wrinkled" surface topology predicts that Ca2+ concentrations up to 80 microM can persist within the folds of membranes for significant times. This intra-wrinkle location may account for 5% of the total cell volume. Using different geometries of wrinkles, our simulations show that high Ca2+ microdomains will be generated most effectively by long narrow membrane wrinkles of similar dimensions to those found experimentally. This is a new concept which has not previously been considered, but which has ramifications as the intra-wrinkle location is also a strategic location at which Ca2+ acts as a regulator of the cortical cytoskeleton and plasma membrane expansion.

KW - Animals

KW - Calcium Signaling

KW - Cell Shape

KW - Cell Surface Extensions

KW - Computer Simulation

KW - Cytoskeleton

KW - Humans

KW - Membrane Microdomains

KW - Models, Theoretical

KW - Neutrophils

U2 - 10.1016/j.ceca.2010.01.005

DO - 10.1016/j.ceca.2010.01.005

M3 - Journal article

C2 - 20153895

VL - 47

SP - 339

EP - 349

JO - Cell Calcium

JF - Cell Calcium

SN - 0143-4160

IS - 4

ER -