Vahid Sheikhhassani
Senior Research Scientist, LACDR
Vahid Sheikhhassani is a Senior Research Scientist within the Medical Systems Biophysics and Bioengineering Lab at the Leiden Academic Centre for Drug Research, Leiden University, working at the crossroads of biophysics and pharmacology. His research centres on developing mechanical markers that distinguish healthy from pathogenic states across scales, from single molecules to living cells.
He established expertise in single-cell force spectroscopy, using optical and acoustic tweezers to characterise the viscoelastic properties of human blood and immune cells under physiological conditions. His work demonstrated how drugs and chemokines modulate cellular mechanics, revealing their potential as physical biomarkers for disease progression and therapeutic response.
In parallel, he combined molecular dynamics simulations with circuit topology and single-molecule analysis to decode the conformational dynamics of intrinsically disordered proteins, including the androgen receptor N-terminal domain implicated in prostate cancer and Kennedy's disease, work with direct implications for targeted drug design.
More recently, Sheikhhassani has expanded into biomolecular condensates. Using scanning probe microscopy, his work, published in Nature Communications (2026), developed novel assays to probe condensate droplet fusion dynamics and mechanical transitions, opening avenues for condensate-targeted therapeutics and bio-inspired material design.
Across his career, Sheikhhassani has leveraged biophysical insights to advance disease understanding and diagnosis.
Presentation: Scanning Probe Methods for Biomolecular Condensate Analysis: Enabling Technologies for Drug Discovery
Biomolecular condensates, membrane-less organelles formed through liquid-liquid phase separation, have emerged as key regulators of cellular function and as a novel class of drug targets. Understanding their material properties and mechanical transitions is critical for developing condensate-targeting therapeutics, yet the tools to probe these properties at physiologically relevant scales have remained limited.
Here, we present scanning probe microscopy (SPM) as an enabling platform for condensate analysis in a drug discovery context. We demonstrate SPM-based assays that quantify condensate viscoelastic properties, mechanical state transitions, and droplet fusion dynamics. Using a nucleic acid-polypeptide model system, we show how UV-induced DNA damage drives liquid-to-solid transitions and arrests droplet coalescence, revealing a direct link between molecular crosslinking and condensate mechanics.
These mechanical readouts provide a new layer of information for characterising condensate behaviour under pathological conditions and in response to candidate therapeutics. By establishing mechanical phenotyping of condensates as a tractable, quantitative approach, this work opens a route toward SPM-based screening platforms that can assess how small molecules modulate condensate material properties, a critical step in the rational design of condensate-targeted drugs.
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