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dc.contributor.authorZou, Guijinen_US
dc.contributor.authorLiu, Yueen_US
dc.contributor.authorGao, Huajianen_US
dc.identifier.citationZou, G., Liu, Y. & Gao, H. (2020). EML webinar overview : Simulation-assisted discovery of membrane targeting nanomedicine. Extreme Mechanics Letters, 39, 100817-.
dc.description.abstractThe COVID-19 pandemic has brought infectious diseases again to the forefront of global public health concerns. In this EML webinar (Gao, 2020), we discuss some recent work on simulation-assisted discovery of membrane targeting nanomedicine to counter increasing antimicrobial resistance and potential application of similar ideas to the current pandemic. A recent report led by the world health organization (WHO) warned that 10 million people worldwide could die of bacterial infections each year by 2050. To avert the crisis, membrane targeting antibiotics are drawing increasing attention due to their intrinsic advantage of low resistance development. In collaboration with a number of experimental groups, we show examples of simulation-assisted discovery of molecular agents capable of selectively penetrating and aggregating in bacterial lipid membranes, causing membrane permeability/rupture. Through systematic all-atom molecular dynamics simulations and free energy analysis, we demonstrate that the membrane activity of the molecular agents correlates with their ability to enter, perturb and permeabilize the lipid bilayers. Further study on different cell membranes demonstrates that the selectivity results from the presence of cholesterol in mammalian but not in bacterial membranes, as the cholesterol can condense the hydrophobic region of membrane, preventing the penetration of the molecular agents. Following the molecular penetration, we establish a continuum theory and derive the energetic driving force for the domain aggregation and pore growth on lipid membrane. We show that the energy barrier to membrane pore formation can be significantly lowered through molecular aggregation on a large domain with intrinsic curvature and a sharp interface. The theory is consistent with experimental observations and validated with coarse-grained molecular dynamics simulations of molecular domain aggregation leading to pore formation in a lipid membrane. The mechanistic modelling and simulation provide some fundamental principles on how molecular antimicrobials interact with bacterial membranes and damage them through domain aggregation and pore formation. For treating viral infections and cancer therapy, we discuss potential size- and lipid-type-based selectivity principles for developing membrane active nanomedicine. These studies suggest a general simulation-assisted platform to accelerate discovery and innovation in nanomedicine against infectious diseases. EML Webinar speakers are updated at
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.description.sponsorshipNanyang Technological Universityen_US
dc.relation.ispartofExtreme Mechanics Lettersen_US
dc.rights© 2020 Elsevier Ltd. All rights reserved.en_US
dc.subjectEngineering::Mechanical engineeringen_US
dc.titleEML webinar overview : Simulation-assisted discovery of membrane targeting nanomedicineen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Mechanical and Aerospace Engineeringen_US
dc.subject.keywordsMembrane Targetingen_US
dc.description.acknowledgementThis work was supported by the U.S. National Science Foundation (Grant CMMI-1562904) and a start-up grant from the Nanyang Technological University and Institute of High Performance Computing, A*STAR, Singapore.en_US
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