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MechanoBody

Research Project
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01.01.2023
 - 31.12.2027

Directing nanoscale particles to strongly adhere to cancer cells and tissues under hydrodynamic flow in vivo is a challenging biophysical problem with important clinical implications. A common approach uses antibodies conjugated to nanoparticles to impart binding specificity, however, when exposed to mechanical shear stress antibodies are known to unbind at extremely low forces (<150 pN)1-3. This problem can occur even when antibodies are selected for high-affinity (e.g., KD < 1 nM) interactions at equilibrium. The goal of this research is therefore to engineer artificial binding proteins that form mechanically stable complexes with their target ligands for applications in nanoparticle-based drug delivery and bioimaging. I will focus on non-antibody (nAb) binding scaffolds (e.g., anticalin, affibody and DARPin) that will be optimized through two disparate yet complementary approaches: (1) geometrics and (2) genetics. By mechanically enhancing binding interactions, I will pioneer a new paradigm in the molecular engineering field called 'MechanoBodies' that will enable enhanced labelling and cargo delivery to cells under high shear stress.

Funding

MechanoBody

Horizon 2020 ERC (GrantsTool), 01.2023-12.2027 (60)
PI : Nash, Michael.

Members (1)

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Michael Nash

Principal Investigator