Environmental Fluctuations and Stochastic Resonance in Protein Folding

Abstract

Stochastic resonance is a mechanism whereby a weak signal becomes detectable through the addition of noise. It is common in many macroscopic biological phenomena, but here we ask whether it can be observed in a microscopic biological phenomenon, protein folding. We investigate the folding kinetics of the protein VlsE, with a folding relaxation time of ca. 0.7 seconds at 38 °C in vitro. First we show that the VlsE unfolding/refolding reaction can be driven by a periodic thermal excitation above the reaction threshold. We detect the reaction by fluorescence from FRET labels on VlSE, and show that accurate rate coefficients and activation barriers can be obtained from modulated kinetics. Then we weaken the periodic temperature modulation below the reaction threshold, and show that addition of artificial thermal noise speeds up the reaction from an undetectable to a detectable rate. We observe a maximum in the recovered signal as a function of thermal noise, a stochastic resonance. Simulation of a small model-protein, analysis in an accompanying theory paper, and our experimental result here all show that environmental noise is a physically and chemically plausible mechanism by which cells could modulate biomolecular dynamics as part of threshold processes such as signaling.

Specific Interactions and Environment Flexibility Tune Protein Stability under Extreme Crowding

“…The investigation of the role of the solvent, metabolites, as well as the fluctuations of the crowding environment in vivo represent future research prospects.…”

“…Alternatively, it is possible to generate solution states where the crowders are either placed in folded or unfolded conformations so as to mimic the extreme two-state environmental conditions. The investigation of the role of the solvent, metabolites, as well as the fluctuations of the crowding environment in vivo 59 represent future research prospects.…”

Live Cell Microscopy: A Physical Chemistry Approach

“…In the auditory perception of all animals, detection of such signal is achieved by a process called stochastic resonance. Stochastic resonance is defined as noise-assisted signal enhancement in a nonlinear system, and it is widely used in signal processing, communications, and control. − Transmission of sensory signal to the brain involves action potentials or spikes of neurons, and the signal is coded in the time intervals between the spikes. − Apart from the neuron network, the same algorithm has been applied to gene expression, , protein folding, − protein synthesis, red-ox processes in cytochrome c, NO reduction on platinum surface, actin transport, and fluctuation among different forms in supercooled water . We had applied the same algorithm and detected dramatic differences in gene silencing between a cancer cell (MCF7) and a normal cell (MCF10A) of human breast cell. , …”

T-cell Receptor Is a Threshold Detector: Sub- and Supra-Threshold Stochastic Resonance in TCR-MHC Clusters on the Cell Surface

“…This implies that the scanning TCR should pick out the wanted cognate pMHC from a highly crowded field of noncognate pMHCs and another receptor. Molecular crowding has been shown to accelerate protein folding reactions, such as the conformational change of TCR, necessary for threshold crossing [76][77][78]. According to this folding picture, the momentarily or previous interactions of the TCR with the crowded neighborhood set the TCR into unspecific, subthreshold conformational oscillations at a lot of frequencies, from which a given, specifically loaded pMHC can select for, according to its vibrational eigenfrequency.…”