Temporal dynamics in an immunological synapse: role of thermal fluctuations in signaling

Daniel R. Bush, Amit K. Chattopadhyay

Research output: Contribution to journalArticle

Abstract

The article analyzes the contribution of stochastic thermal fluctuations in the attachment times of the immature T-cell receptor TCR: peptide-major-histocompatibility-complex pMHC immunological synapse bond. The key question addressed here is the following: how does a synapse bond remain stabilized in the presence of high-frequency thermal noise that potentially equates to a strong detaching force? Focusing on the average time persistence of an immature synapse, we show that the high-frequency nodes accompanying large fluctuations are counterbalanced by low-frequency nodes that evolve over longer time periods, eventually leading to signaling of the immunological synapse bond primarily decided by nodes of the latter type. Our analysis shows that such a counterintuitive behavior could be easily explained from the fact that the survival probability distribution is governed by two distinct phases, corresponding to two separate time exponents, for the two different time regimes. The relatively shorter timescales correspond to the cohesion:adhesion induced immature bond formation whereas the larger time reciprocates the association:dissociation regime leading to TCR:pMHC signaling. From an estimate of the bond survival probability, we show that, at shorter timescales, this probability PΔ(τ) scales with time τ as a universal function of a rescaled noise amplitude DΔ2, such that PΔ(τ)∼τ-(ΔD+12),Δ being the distance from the mean intermembrane (T cell:Antigen Presenting Cell) separation distance. The crossover from this shorter to a longer time regime leads to a universality in the dynamics, at which point the survival probability shows a different power-law scaling compared to the one at shorter timescales. In biological terms, such a crossover indicates that the TCR:pMHC bond has a survival probability with a slower decay rate than the longer LFA-1:ICAM-1 bond justifying its stability.

Original languageEnglish
Article number012706
Number of pages8
JournalPhysical Review E
Volume92
DOIs
Publication statusPublished - 6 Jul 2015

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synapses
Synapse
Fluctuations
Survival Probability
Time Scales
T-cells
Crossover
Vertex of a graph
crossovers
Equate
Survival Distribution
Universal Function
Cohesion
Time-average
Adhesion
cohesion
Decay Rate
thermal noise
Peptides
Persistence

Bibliographical note

© APS

Cite this

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Temporal dynamics in an immunological synapse : role of thermal fluctuations in signaling. / Bush, Daniel R.; Chattopadhyay, Amit K.

In: Physical Review E, Vol. 92, 012706, 06.07.2015.

Research output: Contribution to journalArticle

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