# Continuous Probing of Nanoconstruct-Cell Interactions at Biologically Relevant Time Scales

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2023 · $304,184

## Abstract

PROJECT SUMMARY
 This renewal application builds on our discovery that the shape of nanoparticle-based constructs—what we
define as structural valency—plays a key role in preserving the targeting ligand characteristics of nanoconstructs
even when coated by a protein corona. Protein corona formation and its impact on engineered physicochemical
properties of nanoconstructs has been somewhat controversial but is generally accepted to affect cell and tissue
targeting specificity and downstream biological effects. Using single-particle, live-cell imaging investigations, we
found that the protein corona composition of an ensemble of nanoconstructs was superseded by single-particle
shape effects. Compared to their spherical counterparts, nanoconstructs with branched structures retained their
ligand shell targeting capabilities both on cell membranes and within cells and cellular compartments. Statistically
significant differences in the time-resolved dynamics of differently shaped nanoconstructs interacting with cellular
components cannot be attributed to very minimal variations in protein corona composition.
 We aim to determine the mechanism for how branched nanoconstructs maintain their targeting functionality
in biological environments and then to modulate the spatial organization of the single-particle protein corona with
light during live-cell interactions. We will tune the nanoscale features of the branched nanoconstructs, including
overall size, branch length, and tip radii of curvature, to be commensurate with membrane receptor dimerization
and curvature-induced endosomal signaling and will image interactions at the single-particle level. The specific
aims include (1) Understand how nanoconstruct design and optical stimuli can manipulate the protein corona at
the single-particle level; (2) Investigate structural multivalency of membrane-targeting branched nanoconstructs
on receptor dimerization; (3) Improve intracellular targeting and delivery using branched nanoconstruct shapes.
This work is expected to be of high impact for precision nanomedicine by the intersection of single-nanoparticle
advances with mechanistic insight into biological responses. Our ability to resolve nanoparticle-cell interactions
at relevant time and length scales for receptor recognition and internalization will benefit knowledge in protein
dimerization and nanoscale curvature effects and deepen understanding of endocytosis and immunomodulatory
responses—key processes for advancements in vaccine design and drug delivery.

## Key facts

- **NIH application ID:** 10658552
- **Project number:** 2R01GM131421-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Teri Wang Odom
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $304,184
- **Award type:** 2
- **Project period:** 2019-09-27 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10658552

## Citation

> US National Institutes of Health, RePORTER application 10658552, Continuous Probing of Nanoconstruct-Cell Interactions at Biologically Relevant Time Scales (2R01GM131421-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10658552. Licensed CC0.

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