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Cellular Uptake of Nanoparticles is Regulated by Integrin-Based Adhesion to the Extracellular Matrix
Sailesti Joshi1, Ananya Naha1, Justice Ene1
1Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, 2525 Pottsdamer Street, Tallahassee, Florida 32310, United States.
ACS Applied Materials & Interfaces
|January 6, 2026
Summary
Extracellular matrix coatings on substrates significantly influence how cells interact with and absorb therapeutic nanoparticles (PLGA). Specific coatings like fibronectin and collagen enhance nanoparticle uptake by promoting cell adhesion and cytoskeletal organization, crucial for regenerative medicine.
Area of Science:
- Biomaterials Science
- Cell Biology
- Nanotechnology
- Regenerative Medicine
Background:
- Therapeutic nanoparticle delivery is vital for diverse biomedical applications, including drug delivery and tissue engineering.
- Nanoparticle uptake is influenced by cell-substrate interactions, particularly the extracellular matrix (ECM) and cellular mechanosensing.
- Cell-ECM interactions modulate integrin signaling, focal adhesion formation, and cytoskeletal dynamics, impacting nanoparticle internalization.
Purpose of the Study:
- To investigate how different ECM and ECM-mimetic coatings affect the uptake of poly(lactic-co-glycolic acid) (PLGA) nanoparticles.
- To determine the role of cell-substrate interactions, specifically focal adhesion formation and cytoskeletal organization, in nanoparticle uptake.
- To compare nanoparticle uptake across distinct cell types with varying focal adhesion maturation.
Main Methods:
- Characterization of ECM coatings (collagen I, fibronectin, laminin, hyaluronic acid, poly-l-lysine) using quartz crystal microbalance with dissipation (QCM-D) and ellipsometry.
- Assessment of cell proliferation, spreading, and focal adhesion formation on coated substrates.
- Quantification of PLGA nanoparticle uptake via live-cell imaging and uptake studies using cytochalasin-D to probe actin cytoskeleton dependence.
Main Results:
- Fibronectin (FN) and collagen I (COL) coatings significantly enhanced cell adhesion, proliferation, and focal adhesion formation, leading to higher nanoparticle uptake.
- Hyaluronic acid (HA) and laminin (LM) coatings resulted in reduced cell adhesion and nanoparticle uptake.
- Cell types with more mature focal adhesions (fibroblasts, ASCs) exhibited higher nanoparticle uptake compared to macrophages (RAW264.7).
- Nanoparticle uptake was dependent on the actin cytoskeleton, indicating involvement of actin-dependent endocytic pathways.
Conclusions:
- ECM coating properties and cell type-specific focal adhesion formation critically regulate substrate-mediated nanoparticle uptake.
- FN and COL coatings promote sustained nanoparticle uptake, while LM shows rapid early uptake, highlighting dynamic uptake kinetics.
- These findings offer insights for designing optimized substrate-based nanoparticle delivery systems for regenerative medicine and therapeutic applications.
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