Substrate Stiffness Regulates Cellular Uptake of Nanoparticles

• Published in: Nano letters Vol. 13; no. 4; pp. 1611 - 1615
• Main Authors: Huang, Changjin, Butler, Peter J, Tong, Sheng, Muddana, Hari S, Bao, Gang, Zhang, Sulin
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 10.04.2013
• Subjects: Acrylic Resins - chemistry; Animals; Aorta - cytology; Aorta - drug effects; Biological and medical sciences; Biotechnology; Cattle; Cellular; Condensed matter: structure, mechanical and thermal properties; Cross-disciplinary physics: materials science; rheology; Drug Delivery Systems - methods; Endothelial Cells - cytology; Endothelial Cells - drug effects; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Materials science; Mathematical models; Mechanical and acoustical properties of condensed matter; Mechanical properties of nanoscale materials; Membranes; Methods. Procedures. Technologies; Nanocrystalline materials; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Nanoscale materials and structures: fabrication and characterization; Nanostructure; Neoplasms - drug therapy; Others; Physics; Stiffness; Substrate Specificity; Surface Properties; Thermal properties of condensed matter; Thermal properties of small particles, nanocrystals, nanotubes; Thermodynamic models; Uptakes; Various methods and equipments; Substrate stiffness; cancer therapy; nanoparticles; cellular spreading; membrane tension; cellular uptake; Endothelial cell; Tumor cells; Theoretical study; Drug carrier; Optimization; Nanoparticles; In vivo; Experimental result; Fluorescent material; Thermodynamic model; Modelling; Stiffness; Hydrogel; Nanostructured materials; Quantitative chemical analysis; Medical application
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/nl400033h

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 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 that 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.