Advancing the understanding of membrane fusion through a computational platform based on continuum mechanics models
Abstract
The purpose of the project is to advance the development of a computational platform for in silico studies of drug delivery processes involving membrane fusion. The computational methodology is based on novel mathematical models derived from principles of continuum mechanics and thermodynamics. Liposomes are lipid vesicles with a bilayered membrane structure that have been widely used as carriers for drug delivery. Despite the extensive experimental research behind liposomes, only a few liposomal systems have been approved by the U.S. Food and Drug Administration for clinical use. One of the reasons is that a thorough understanding of the complex biophysics involved in drug delivery and uptake is still lacking. The use of mathematical modeling and computational simulations to support and complement experimental evidence in this field is scarce and not nearly as wide-spread as in other scientific disciplines. My collaborators (Dr. Olshanskii, UH Math, and Dr. Majd, UH Bioengineering) and I have been working to fill this gap. We are developing a computational platform, which includes novel continuum models, numerical algorithms and data analysis tools, to support and guide experimental practice in elucidating an uptake mechanism: liposomal fusion into cells. Our approach builds on the modeling, analysis, and computational work on continuum models formulated in terms of partial differential equations posed on surfaces and fluid-structure interaction problems, and benefits from an on-going collaboration with Dr. Majd, a biomedical engineer at UH specialized in membrane models for biophysical studies and nano-particulate delivery systems.
Principal Investigator
Dr. A. Quaini, University of Houston
Collaborators
Dr. M. Olshanskii, University of Houston
Dr. S. Majd, University of Houston
Student Involved in the Project
Alexander Zhiliakov, Graduate student (UH)
Vladimir Yushutin, Post-Doc (UH)
Publications
- A. Zhiliakov, Y. Wang, A. Quaini, M. Olshanskii, S. Majd: Experimental validation of a phase-field model to predict coarsening dynamics of lipid domains in multicomponent membranes, BBA - Biomembranes, 1863(1):183446, 2021.
arXiv:2006.14125 | link - V. Yushutin, A. Quaini, M. Olshanskii: Numerical modelling of phase separation on dynamic surfaces, J. Comput. Phys., 407:109126, 2020.
link | arXiv:1907.11314 - V. Yushutin, A. Quaini, S. Majd, M. Olshanskii: A computational study of lateral phase separation in biological membranes, Int. J. Num. Meth. Biomed. Eng., 35(3):e3181, 2019.
link | arXiv:1808.06741 - M. Olshanskii, A. Quaini, A. Reusken, V. Yushutin: A finite element method for the surface Stokes problem, SIAM J. Sci. Comput., 40(4):A2492-A2518, 2018.
link | arXiv:1801.06589