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Substrate Stiffness Regulates Cellular Uptake of Nanoparticles

Changjin Huang (The Pennsylvania State Univers), Peter Butler (Pennsylvania State University), Sheng Tong (Georgia Institute of Technology and Emory University), Hari Muddana (The Pennsylvania State University), Gang Bao (Georgia Institute of Technology and Emory University), Sulin Zhang (Penn State University)

Mechanics and Physics of Biological Cells

Tue 10:45 - 12:15

Barus-Holley 141

Nanoparticle (NP)-bioconjugates hold great promise for more sensitive disease diagnosis and more effective anticancer drug delivery compared with existing approaches. A critical aspect in both applications is cellular internalization of NPs, which is influenced by NP properties and cell surface mechanics. Despite considerable progress in the optimization of the NP-bioconjugates for improved targeting, the role of substrate stiffness on cellular uptake has not been investigated. Using polyacrylamide (PA) hydrogels as model substrates with tunable stiffness, we quantified the relationship between substrate stiffness and cellular uptake of fluorescent NPs by bovine aortic endothelial cells (BAECs). We found that a stiffer substrate results in a higher total cellular uptake on a per cell basis, but a lower uptake per unit membrane area. To obtain a mechanistic understanding of the cellular uptake behavior, we developed a thermodynamic model which predicts that membrane spreading area and cell membrane tension are two key factors controlling cellular uptake of NPs, both of which are modulated by substrate stiffness. Our experimental and modeling results not only open up new avenues for engineering NP-based cancer cell targets for more effective in vivo delivery, but also contribute an example of how the physical environment dictates cellular behavior and function.