The Secret Lives of Fluorescent Membrane Probes as Revealed by Molecular Dynamics Simulations

Abstract

Fluorescent probes have been employed for more than half a century to study the structure and dynamics of model and biological membranes, using spectroscopic and/or microscopic experimental approaches. While their utilization has led to tremendous progress in our knowledge of membrane biophysics and physiology, in some respects the behavior of bilayer-inserted membrane probes has long remained inscrutable. The location, orientation and interaction of fluorophores with lipid and/or water molecules are often not well known, and they are crucial for understanding what the probe is actually reporting. Moreover, because the probe is an extraneous inclusion, it may perturb the properties of the host membrane system, altering the very properties it is supposed to measure. For these reasons, the need for independent methodologies to assess the behavior of bilayer-inserted fluorescence probes has been recognized for a long time. Because of recent improvements in computational tools, molecular dynamics (MD) simulations have become a popular means of obtaining this important information. The present review addresses MD studies of all major classes of fluorescent membrane probes, focusing in the period between 2011 and 2020, during which such work has undergone a dramatic surge in both the number of studies and the variety of probes and properties accessed.

How to best estimate the viscosity of lipid bilayers

“…Since the value of a bilayer viscosity is characteristic of the membrane it should be independent of inclusion size, and it should not be affected by the addition of a fluorescent probe. The later has been corroborated by molecular dynamics simulations [42,43], which show that the addition of a probe has a minimal effect on bilayer viscosity. An identical value should be derived for a bilayer viscosity regardless of the size of a diffusing inclusion embedded into this bilayer.…”

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

“…Fluorescent labels [514][515][516][517][518][519][520][521][522][523][524][525][526][527][528][529] Fragrance Musk xylene [132] 2-aminoethoxydiphenyl borate (inhibitor of IP 3 receptors and TRP channels) [530] Organic solvents…”

Multiscale simulations of polyzwitterions in aqueous bulk solutions and brush array configurations

“…The relevant time and length scales governing the thermodynamics and dynamics of long-chain polyzwitterions in solution, their adsorption or chemical grafting onto solid surfaces, and their antifouling action exceed by far the range of microseconds and tens of nanometers that can be addressed by atomistic simulations on readily available computational platforms; 26,27 judicious coarse-graining is thus necessary.…”