Complementary biophysical tools to investigate lipid specificity in the interaction between bioactive molecules and the plasma membrane: A review

Abstract

Plasma membranes are complex entities common to all living cells. The basic principle of their organization appears very simple, but they are actually of high complexity and represent very dynamic structures. The interactions between bioactive molecules and lipids are important for numerous processes, from drug bioavailability to viral fusion. The cell membrane is a carefully balanced environment and any change inflicted upon its structure by a bioactive molecule must be considered in conjunction with the overall effect that this may have on the function and integrity of the membrane. Conceptually, understanding the molecular mechanisms by which bioactive molecules interact with cell membranes is of fundamental importance. Lipid specificity is a key factor for the detailed understanding of the penetration and/or activity of lipid-interacting molecules and of mechanisms of some diseases. Further investigation in that way should improve drug discovery and development of membrane-active molecules in many domains such as health, plant protection or microbiology. In this review, we will present complementary biophysical approaches that can give information about lipid specificity at a molecular point of view. Examples of application will be given for different molecule types, from biomolecules to pharmacological drugs. A special emphasis is given to cyclic lipopeptides since they are interesting molecules in the scope of this review by combining a peptidic moiety and a lipidic tail and by exerting their activity via specific interactions with the plasma membrane.

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

“…36 paramagnetic resonance (EPR) [40]. Indirectly, the effects can also be determined using anisotropy studies, where changes in the rotational movement of a membrane probe reflect the influence of a drug on the membrane fluidity [239,268].…”

“…Some techniques will be covered in this review (see chapter 3 and 4). For a full description of the preparation methods of the models and the protocols for the experimental techniques, please see the following reviews [9,14,40].…”

Biophysics in cancer: The relevance of drug-membrane interaction studies

“…A brief description of the most used biomimetic models in the context of the study of anticancer drugs-membrane interactions is given below. More detailed information about these and other biomembrane models can the found in the following reviews [45,48].…”

Membrane Active Peptides and Their Biophysical Characterization

“…Binding isotherms of peptide-lipid systems can be measured by FRET using labeled peptide as the donor and labeled lipid as the receptor while FCS analysis provides information about the diffusion coefficients and rates of fluorophore transitions [199,[245][246][247]. Specifically, with FRET it is possible to monitor the entry and then quantify the ratio of CPPs in the membranes [68].…”