Presentation by B. García Rodríguez at SPIE-ETAI, San Diego, 5 August 2025

Biomolecular condensates are analyzed and characterized using a holographic microscope, which utilizes a variational autoencoder (VAE) to quantify size, protein concentration, and the sharpness of the RNA-binding protein interface. (Image by B. Garcia.)
Structure and dynamics of biomolecular condensates revealed by deep learning enhanced interferometric microscopy
Berenice García Rodríguez, Makasewicz Katarzyna, Giovanni Volpe, Paolo Arosio, Daniel Sundås Midtvedt.
Date: 5 August 2025
Time: 5:00 PM – 5:15 PM PDT
Place:
Conv. Ctr. Room 4
Presentation type:
Oral

Biomolecular condensates are biological structures that form through weak, multivalent interactions primarily between low complexity domains of intrinsically disordered proteins, existing in cells as submicrometer structures. Their functions rely sensitively on physical properties such as size, internal protein concentration, and interfacial tension. However, direct measurements of these properties in submicrometer condensates remain scarce. In this work, we employ deep learning enhanced interferometric imaging to quantify size, protein concentration, and the sharpness of the interface of submicrometer condensates formed by the low complexity domain of the RNA-binding protein DDX4-LCD. We find that, within the two-phase region, DDX4-LCD forms spherical condensates with an internal protein concentration that can be slightly modulated by adding salt to the solution. Furthermore, we find that multiple populations of protein clusters coexist in the sample, some persisting even outside the two-phase region of the phase diagram, separable by their interface properties and dynamics. This hints at a more complex phase diagram of DDX4-LCD condensation than previously anticipated.

 

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