Dissertation
Computational Study of Receptor Mediated Endocytosis for Functional Nanoparticle Transport
Washington State University
Doctor of Philosophy (PhD), Washington State University
2023
DOI:
https://doi.org/10.7273/000005343
Abstract
Receptor mediated endocytosis (RME) is a frequently observed process used by bioparticles such as viruses, bacteria, and therapeutic drugs to enter cells. Traditionally, it was assumed that RME was always facilitated by the coat protein clathrin, but recent research has shown that there are also clathrin-independent RME pathways. These pathways are crucial for understanding how viruses, bacteria, and drugs enter cells as well as for delivering drugs to the affected cells. However, RME is a complex and multi-stage process that involves intricate interactions between the particles and cellular components, and therefore extensive research is needed. Numerous computational models have been proposed to augment experimental findings, but a comprehensive understanding of endocytic pathways remains challenging and elusive.This study utilized a stochastic model based on the Metropolis Monte Carlo method to investigate the internalization of nanoparticles into cells. The model takes into account ligand- receptor interactions, the formation of clathrin-coated pits, and membrane deformation during receptor-mediated endocytosis (RME). The model was used to examine the impact of critical physiochemical parameters, including the flexural rigidity and length of receptors, and the reaction cutoff distance, on both clathrin-dependent and clathrin-independent RME.
Furthermore, while spherical nanoparticles are currently the most commonly used nanocarriers in laboratory and clinical settings, advances in nanofabrication techniques have made it possible to create nanoparticles of various shapes that closely resemble viruses and bacteria found in nature. The development of nonspherical nanoparticles holds great promise for future drug delivery systems. Therefore, we expanded our model to explore the design considerations and overall endocytosis efficiency of rod-shaped nanoparticles in comparison to their spherical counterparts.
Finally, our simulation of the endocytosis process highlighted the significant impact of various physical, mechanical, and chemical factors, and a comprehensive study of these parameters can be an extensive undertaking. Therefore, incorporating more sophisticated computational algorithms during the simulation, or for post-processing the simulation results, holds promise. To explore this direction in future research, we have demonstrated a novel physics-based machine learning approach on a classic heat transfer problem in this study.
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Details
- Title
- Computational Study of Receptor Mediated Endocytosis for Functional Nanoparticle Transport
- Creators
- Md Muhtasim Billah
- Contributors
- Jin Liu (Advisor)Prashanta Dutta (Committee Member)Yuehe Lin (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Mechanical and Materials Engineering, School of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 150
- Identifiers
- 99901031140001842
- Language
- English
- Resource Type
- Dissertation