(598d) Computational Study of Deformable Functionalized Nanocarrier Adhesion to the Cell Surface

A functionalized nanocarrier (NC) adheres to its target cell through the multivalent interactions of its surface ligands with their corresponding cell surface receptors. The binding efficacy of the NC is governed by a complex set of physico-chemical and physiological parameters, that include its shape, size, and surface chemistry, the receptor expression levels, the chemical composition and the mechanical state of the target cell membrane, and the flow conditions and the thickness of the glycocalyx layer in the vicinity of the target site. Rational design and optimization of functionalized NCs require a fundamental understanding of the interplay between these seemingly disparate factors. New classes of NCs possess unique and exquisite chemistries for which rational design principles are quite distinct from rigid and regular-shaped NCs.

We focus on the adhesion of deformable crosslinked polymer based NCs functionalized with antibodies to receptors on the cell membrane. We have developed a computational framework by accounting for the mechanical properties of the NC and its emergent shape on the multivalency of binding. The complex interplay between various energetic and entropic contributions in the system results in the avidity of the functionalized NC. In particular, in a recent study for a rigid NC, the importance of the loss in translational entropy of receptor motion and the change in entropy of the cell membrane undulations were demonstrated as crucial factors that define NC avidity in a cell-type dependent fashion [1]. In this study, a third dimension is explored to this problem by considering the NC flexibility. We systematically vary the contributions of the NC conformational entropy in the case of NC with different crosslinks, to show effect of crosslinking on the NC adhesion free energy landscape. We address how the NC binding is sensitive to NC composition from very soft, deformable NCs to rigid spheres and how the interplay between the entropic terms of the deformable NC and the cell membrane undulations play a significant role on the enhancement of the NC avidity.

We acknowledge funding from the National Institutes of Health through grants NIBIB 1R01EB006818 and 1U01EB016027.

[1] Ramakrishnan et. al. (2016). Biophysically inspired model for functionalized nanocarrier adhesion to cell surface: roles of protein expression and mechanical factors. J. Royal Society Open Science, 3, 160260.