Biophysical Society Thematic Meeting| Padova 2019

Quantitative Aspects of Membrane Fusion and Fission

Poster Abstracts

54-POS Board 54 THE ROLE OF SPECIFIC LYSOSOMAL LIPID - BIS(MONOACLYGLYCERO)PHOSPHATE (BMP) - ON MEMBRANE FUSION AND

ITS ASSOCIATION WITH ACID ENVIRONMENT Tayana M. Tsubone 1 ; Ana Paula Ramos 2 ; Rosangela Itri 1 ; 1 University of Sao Paulo, Institute of Physics, São Paulo, Brazil

2 University of Sao Paulo, Department of Chemistry, Ribeirão Preto, São Paulo, Brazil The autophagic/lysosomal system includes a variety of vesicular compartments that undergo dynamic fusion events. It because during autophagy, cytoplasmic materials are sequestered by the autophagosome and transported to the lysosome for digestion. The specific stages of autophagy are induction, formation of the isolation membrane (phagophore), formation and maturation of the autophagosome and, finally, fusion with a late endosome or lysosome. However, the characteristics and factors modulating these autophagosome– lysosome fusion remain, for the most part, unknown. Koga and co-workers suggested that changes in the lipid composition may inhibits autophagic vesicular fusion. However, the complexity of vesicular fusion events that take place in autophagy, makes it difficult to study in intact cells. To gain insights on the properties that govern membrane lysosomal fusion events, we have investigated the biophysical properties of mimetic membranes that contains bis(monoaclyglycero)phosphate (BMP) - a hallmark phospholipid of lysosomal membranes - and their consequences on membrane fusion. Considering that BMP has a unique structural characteristic, here we have used DOPG (that is a structural isomer of BMP) for comparison purpose. Interestingly, our results have shown that membrane fusion is significantly influenced by pH, unlikely the data from DOPG vesicles. The explanation for this phenomena can be related to properties of BMP on packing membranes differently at low pH. Surface pressure vs surface area isotherms obtained from Langmuir monolayers of BMP in pH 4.5 indicates that the surface pressure rises more slowly than in BMP pH 7.4 isotherm suggesting that the presence of protons on the head group disturbs lipid film packing and reduce the surface area available for each molecule due their higher compaction. In fact, at pH 4, BMP exhibits lower surface charge density than DOPG, indicating that the decreased electrostatic repulsion on the charged head groups of BMP. Acknowledgements. Thanks FAPESP for financial support with scholarship grant (2016/23071- 9) and R.I. acknowledges CNPq research fellowship.

113