Computational study of multivalent binding of deformable nanocarriers to the cell surface inspired by a soft matter approach

Functionalized nanocarriers (NCs) adhered to the target cell through multivalent interactions of their surface ligands with their corresponding cell surface receptors promise to revolutionize the biomedical field for drug delivery and remote–sensing diagnostic applications. The binding efficacy of the NC is governed by a complex set of physicochemical and physiological parameters that include its shape, size, and surface chemistry, the receptor expression levels and the mechanical state of the cell membrane and relatively little is known about the role of carrier flexibility on drug delivery.

We focus on the adhesion of deformable crosslinked polymeric NCs to receptors on the cell membrane. We have developed a statistical mechanics-based mesoscale model by accounting for the mechanical properties of the NC and the cell membrane, the configurational degrees of freedom of the NC, membrane and receptor-ligand interactions. The emergent properties of the model are obtained using Monte Carlo simulations and free energy calculations. We address how the NC binding is sensitive to NC composition from very soft NC to rigid sphere and how the interplay between energetic and entropic terms of NCs, the cell membrane and the receptors play a role on the enhancement of the NC avidity.