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Heightened sensitivity of a lattice of membrane receptors
1Institut Curie, Physico Chimie Curie, Section de Recherche, 26 rue d'Ulm, 75231 Paris Cedex 05, France. td18@cam.ac.uk
Abstract:
Receptor proteins in both eukaryotic and prokaryotic cells have been found to form two-dimensional clusters in the plasma membrane. In this study, we examine the proposition that such clusters might show coordinated responses because of the spread of conformational states from one receptor to its neighbors. A Monte Carlo simulation was developed in which receptors flipped in probabilistic fashion between an active and an inactive state. Conformational energies depended on (i) ligand binding, (ii) a chemical modification of the receptor conferring adaptation, and (iii) the activity of neighboring receptors. Rate constants were based on data from known biological receptors, especially the bacterial Tar receptor, and on theoretical constraints derived from an analogous Ising model. The simulated system showed a greatly enhanced sensitivity to external signals compared with a corresponding set of uncoupled receptors and was operational over a much wider range of ambient concentrations. These and other properties should make a lattice of conformationally coupled receptors ideally suited to act as a "nose" by which a cell can detect and respond to extracellular stimuli.
Insights
Cell receptors form clusters that coordinate responses. This simulation shows coupled receptors act like a biological "nose," enhancing cellular detection of external signals.
Area of Science:
- Cellular biology
- Biophysics
- Computational biology
Background:
- Receptor proteins in cell membranes often form 2D clusters.
- These clusters may exhibit coordinated behavior through conformational state propagation.
Purpose of the Study:
- To investigate if receptor clusters show coordinated responses via neighbor interactions.
- To model the spread of conformational states within receptor lattices.
Main Methods:
- Developed a Monte Carlo simulation for receptor state transitions (active/inactive).
- Incorporated ligand binding, receptor adaptation, and neighbor activity into conformational energies.
- Utilized rate constants from biological receptors (e.g., bacterial Tar receptor) and Ising model constraints.
Main Results:
- Simulated coupled receptors demonstrated significantly enhanced signal sensitivity compared to uncoupled ones.
- The system remained operational across a broader range of ambient concentrations.
- Conformationally coupled receptor lattices exhibited properties suitable for cellular signal detection.
Conclusions:
- Receptor clustering facilitates coordinated cellular responses to external stimuli.
- Coupled receptor lattices can function as a sensitive cellular 'nose' for detecting environmental signals.
- This model provides insights into the biophysical mechanisms underlying cellular sensing.