Poly(N-isopropylacrylamide) (PNIPAM) microgels represent a versatile class of soft nanocarriers with significant potential for biomedical applications, particularly in drug delivery systems. However, the fundamental relationships between microgel physicochemical properties and their behavior at different interfaces—from solid surfaces to biological membranes—remain poorly understood. This thesis systematically investigates microgel characterization across multiple interfaces, establishing crucial structure-property relationships that govern both surface adsorption and cellular interactions. When microgels adsorb at interfaces, they undergo extensive deformation and lateral spreading to minimize unfavorable contacts while maximizing interfacial area with polymer chains. This process becomes particularly complex for microgels with sophisticated architectures, where hollow cavities, rigid cores, or anisotropic shapes introduce additional mechanical constraints and heterogeneities that fundamentally alter their interfacial behavior. Atomic force microscopy emerges as a uniquely powerful tool for investigating these complex deformation processes, enabling nanoscale characterization of mechanical properties under physiologically relevant conditions while simultaneously mapping three- dimensional distributions of stiffness throughout individual particles. The technique’s ability to probe local resistance to deformation provides unprecedented insights into how internal architecture translates into interfacial mechanical signatures. This work systematically examines how small spherical hollow microgels, large anisotropic hollow and core-shell microgels behave during adsorption. The investigations demonstrate how cavity formation, shape anisotropy, and constrained deformation combine to create unique mechanical landscapes that govern adsorption and structure properties. Moreover, the interfacial behavior of microgels serves as a predictive tool for cellular uptake ability. AFM force spectroscopy measurements on surface-adsorbed microgels reveal a remarkable correlation between mechanical properties and cellular internalization behavior using HEK293T cells as a model system. A normalized "relative indentation" parameter successfully predicts cellular uptake across diverse microgel types, identifying three distinct groups: fast uptake (highly deformable particles), intermediate uptake (moderately deformable systems), and no uptake (rigid large microgels). Remarkably, large ultra-low cross-linked microgels (>1 µm diameter) demonstrate successful cellular internalization despite exceeding typical size thresholds, with the fastest internalization time observed across all systems. Additional Post-internalization studies reveal that small microgels progressively accumulate in lysosomes (>75% after 4 hours) without significantly disrupting actin cytoskeleton organization, though modest changes in microtubule network architecture were observed. These findings prove the perspective of usage of microgels in biomedical application especially accompanied with powerful AFM characterization.
Andrey Babenyshev (Thu,) studied this question.