28 May 2017 to 2 June 2017
Queen's University
America/Toronto timezone
Welcome to the 2017 CAP Congress! / Bienvenue au congrès de l'ACP 2017!

Partitioning of Caffeine in Lipid Bilayers Reduces Membrane Fluidity and Increases Membrane Thickness

30 May 2017, 16:30
Miller Hall 105 (Queen's University)

Miller Hall 105

Queen's University

CLOSED - Oral (Student, In Competition) / Orale (Étudiant(e), inscrit à la compétition) Physics in Medicine and Biology / Physique en médecine et en biologie (DPMB-DPMB) T4-7 Biomechanics and Fluid Dynamics (DPMB) | Biomécanique et dynamique des fluides (DPMB)


Adree Khondker (McMaster University)


Caffeine is the most common adjuvant in drug “cocktails”; however, the mechanisms by which the molecule elicits its adjuvant effects remain unknown. The prevalence of membrane mediated drug-lipid interactions for amphiphilic molecules, such as caffeine, is indisputable through membrane partitioning, bioenergetics, and structure. Here, we characterized caffeine’s interactions with cell membranes with respect to hydration with time-resolved X-ray diffraction and Molecular Dynamics simulations [1].

Evidence from both simulation and experiment suggest that caffeine localizes within the head-tail interface of lipid bilayers and increases the thickness of the membrane. By attracting water molecules from neighboring lipid molecules, the partitioning of caffeine leads to the formation of “water pockets”, i.e., a local increase of water density in the head-tail interface. Through this mechanism, caffeine leads to an overall decrease of the gauche defect density in the membranes and an increase of membrane thickness, indicating a loss of membrane fluidity. This provides a mechanism by which caffeine can inhibit drug metabolizing enzymes, such as cytochrome P450, which in turn would increase the bioavailability of primary drugs in active-form.

[1] A Khondker, A Dhaliwal, RJ Alsop, J Tang, M. Backholm, AC Shi, MC Rheinstädter. Phys. Chem. Chem. Phys., 2017, Advance Article, DOI: 10.1039/C6CP08104E

Primary author

Adree Khondker (McMaster University)


Mr Alex Dhaliwal (McMaster University, Department of Physics and Astronomy) Richard Alsop (McMaster University) Jennifer Tang (McMaster University) Matilda Backholm (McMaster University) An-Chang Shi (McMaster University) Maikel Rheinstadter (McMaster University)

Presentation Materials