Aswin Muralidharan

I am a postdoctoral scientist at Delft University of Technology with Stan Brouns, where I study bacterial defense systems against mobile genetic elements.

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For my research, I use microscopy, microfluidics and bioengineering to answer problems in molecular biology and biophysics. Representative papers are highlighted.

We performed a fundamental study of mechanism of co-electrotransfer of oligonucleotides and siRNA simultaneously with plasmid DNA.

Clinical Pseudomonas aeruginosa strains accumulate defense systems to obtain panphage resistance.

We reviewed the latest trends in electrotransfer of nucleic acids and proteins.

We developed charge-reversing polycations which can encapsulate DNA and release it at nucleophilic environments. We further demonstrate evidences that these polycations could potentially be used for gene transfection applications.

In this dissertation: (i) we unravel how actin networks regulate the cell membrane electropermeability, (ii) we reveal the intracellular biophysical transport mechanisms of electrotransferred DNA cargo, (iii) we present a localized electroporation device where cells are trapped in regions of high electric fields by the flow.

After a critical evaluation, we discovered that existing models are insufficient to simulate the transmembrane transport associated with electroporation and hence must be revisited.

We developed microtrap electroporation, and it works better than conventional bulk electroporation to deliver exogenous biomolecules.

We created multi-functional hydrogel based microcarriers inside which we grew three dimensional cancer cell cultures and observed them over several days.

We tracked electrotransferred DNA cargo transport inside mammalian cells and discovered that it is not the DNA size, but what it encounters in the cytosol that governs it's intracellular transport.

We revealed that actin networks increase the energy barrier of electroporation, challenging the traditional view that only lipid bilayer membranes are involved in maintaining cell membrane electropermeability.

We showed that electrotransfer of DNA to giant unilamellar vesicles is independent of DNA size.

We showed that actin networks inside vesicles increase the resealing time after electroporation. Furthermore, the actin networks depolymerize during electroporation.

We studied the flow patterns in a left ventricle model using computational fluid dynamics and statistical shape modelling and compared it with particle image velocimetry experiments.

We validated high frame ultrasound particle image velocimetry using gold standard optical particle image velocimetry.

We use microfluidics to observe the molecular processes involved in breakup of polymeric droplets.