Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Thursday Speaker Abstracts

HALF A CENTURY DECIPHERING MEMBRANE STRUCTURE, DYNAMICS AND FUNCTION BASED ON A COMMENTARY IN BIOPHYSICAL REVIEWS, 13:849–852 (2021) Shirley Schreier 1 ; 1 University of Sao Paulo, Biochemistry, Sao Paulo, Brazil My research on membranes started in 1970, at the National Research Council of Canada. Research during the 70’s revealed the dynamical properties of membranes, and spin labeling EPR contributed greatly to these findings. We studied the effects of cholesterol, ions, and pH on the order and mobility of lipid bilayers and designed a novel experiment to monitor membrane permeability. The lab was among the first to introduce deuterium NMR, providing molecular details of local anesthetics-membrane interactions. My laboratory started in 1973. We were the first to work with liposomes and other phospholipid membranes and to use EPR for this purpose in Brazil. We examined membrane effects on apparent pK of ionizable compounds and on reaction kinetics of membrane-partitioning compounds. Methods were designed to determine partition coefficients. We investigated hemin-membrane interaction and obtained detailed information about aggregation and autoxidation of the polyene antibiotic amphotericin B. Our studies also focused on detergent micelles. The amino acid 2,2,6,6-tetramethyl-N-oxyl-4-amino- 4- carboxylic acid (TOAC) is useful to analyze peptide conformational properties. TOAC can be introduced via a peptide bond at any position in the chain. In angiotensin II and bradykinin, insertion in the middle led to a bend, inactivating the compounds. Since the 1990’s, we mostly focused on peptide-membrane interaction, making additional use of circular dichroism and fluorescence. Our studies with GPCR fragments showed that the peptides tend to acquire a similar conformation to that in the protein. Moreover, they oriented as expected, parallel or perpendicular to the membrane. Sea anemone toxins, and their N-terminal peptides were investigated to understand their leakage-promoting mechanism. Another relevant question is understanding antimicrobial peptide mechanism of action and toxicity. TOAC-labeled analogues of tritrpticin presented a higher therapeutic index than the parent compound, making them interesting drug candidates. I keep working, and I am still fascinated by the wonder of membranes.

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