Charge Modulation at the Liquid Crystal Droplet-Aqueous Interface Enables Ultrasensitive, Nonspecific Protein...

Area of Science:

• Materials Science
• Biophysics
• Analytical Chemistry

Background:

• Thermotropic nematic liquid crystals (LCs) are used for analyte detection, but protein sensing is limited by low sensitivity and reliance on auxiliary molecules.
• Current methods for folded protein detection using LCs typically have micromolar detection limits.

Purpose of the Study:

• To investigate molecular interactions for ultrasensitive protein detection at a liquid crystal (LC) microdroplet/aqueous interface without co-nematogens.
• To establish a foundation for developing versatile and highly specific biomolecular detection platforms using LCs.

Main Methods:

• Utilized UV-treated 5CB liquid crystals and flow-focused microfluidics to create charged microdroplets.
• Introduced model proteins (α-synuclein, α-chymotrypsin, myoglobin, BSA) to observe LC microdroplet defect transitions.
• Employed isothermal titration calorimetry and molecular dynamics simulations to analyze protein-LC interactions.

Main Results:

• Observed rapid radial- to bipolar-defect transitions in LC microdroplets upon protein addition, indicating detection.
• Identified dominant electrostatic force-mediated adsorption of proteins at the LC/aqueous interface.
• Demonstrated that protein surface charge variation via bioconjugation allows tuning of detection limits.

Conclusions:

• Protein adsorption at the LC/aqueous interface, driven by electrostatic forces, enables ultrasensitive detection.
• The findings provide insights for designing responsive LC systems for tailored biomolecular detection.
• This work lays the groundwork for advanced, specific protein detection platforms based on LC microdroplets.