Molecular viewof the interaction of S-methyl methanethiosulfonatewith DPPC bilayer

VIRGINIA MIGUEL; MA. E. DEFONSI LESTARD; MA. E. TUTTOLOMONDO; SONIA B. DÍAZ; AIDA BEN ALTABEF; MARCELO PUIATTI; ADRIANA B. PIERINI

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 1858 p. 38 - 46

0005-2736

agent, S-methyl methanethiosulfonate (MMTS), with a model bilayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC).Weanalyzed and compared its diffusionmechanismswith the relatedmolecule dimethylsulfoxide (DMSO).Weobtained spatially resolved free energy profiles ofMMTS partition into a DPPC bilayer in the liquid-crystallinephase through potential of mean force (PMF) calculations using an umbrella sampling technique. These profilesshowed a minimumforMMTS close to the carbonyl region of DPPC. The location ofMMTS molecules in the DPPCbilayer observed in the MD was confirmed by previous SERS studies [1].We decomposed PMF profiles into entropicand enthalpic contributions. These results showed that the driving force for the partitioning of MMTSinto the upper region of DPPC is driven by a favorable entropy change while partitioning into the acyl chains isdriven by enthalpy. On the other hand, the partition of DMSO into the membrane is not favored, and is drivenby entropy instead of enthalpy. Free diffusion MD simulations using all atom and coarse grained (CG) modelsof DPPC in presence ofMMTSwere used to analyze the effect of DPPC-MMTS interaction. Density profiles showedthatMMTS locates preferentially in the carbonyl region, as expected according to the PMF profile and the experimentalevidence. MMTS presented two differential effects over the packing of DPPC hydrocarbonate chains atlow or at high molar ratios. An ordering effect was observed when a CGMMTS model was used. Finally, free diffusionMD and PMF decomposition for DMSO were used for comparison.