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One possible mechanism is the efflux by protein P-gp, which is found predominantly in cholesterol enriched domains. Thereby, a hypothesis for the vulnerability of doxorubicin to efflux through P-gp is its enhanced affinity for the ordered cholesterol rich regions of the plasma membrane. Thus, we have studied doxorubicin\u2019s interaction with model membranes in a cholesterol rich, ordered environment and in liquid-disordered cholesterol poor environment. We have combined three separate experimental protocols: UV-Vis spectrophotometry, fluorescence quenching and steady-state anisotropy and computational molecular dynamics modeling. Our results show that the presence of cholesterol induces a change in membrane structure and doesn\u2019t impair doxorubicin\u2019s membrane partitioning, but reduces drug\u2019s influence on membrane fluidity without directly interacting with it. It is thus possible that the resistance mechanism that lowers the efficacy of doxorubicin, results from an increased density in membrane regions where the efflux proteins are present. This work represents a successful approach, combining experimental and computational studies of membrane based systems to unveil the behavior of drugs and candidate drug molecules.<\/jats:p>","DOI":"10.1038\/s41598-017-06445-z","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T16:01:28Z","timestamp":1500393688000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Influence of doxorubicin on model cell membrane properties: insights from in vitro and in silico studies"],"prefix":"10.1038","volume":"7","author":[{"given":"Ana Catarina","family":"Alves","sequence":"first","affiliation":[]},{"given":"Aniket","family":"Magarkar","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Horta","sequence":"additional","affiliation":[]},{"given":"Jose L. F. 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