Accelerating Reaction Rates of Biomolecules by Using Shear Stress in Artificial Capillary Systems.

Area of Science:

• Biomimetics and Biophysical Chemistry
• Microfluidics and Chemical Engineering
• Molecular Dynamics and Reaction Kinetics

Background:

• Biomimetics traditionally focuses on nature's chemical tools, neglecting its physical toolkit.
• Understanding physical forces in biological systems is crucial for biomimetic design.
• Emulating capillary-level biophysics can reveal novel chemical insights.

Purpose of the Study:

• To design and investigate biophysically mimetic microfluidic reactors.
• To explore the impact of physical forces, specifically shear stress, on chemical reactions.
• To develop a novel microfluidic approach for biomarker analysis and antibody stability studies.

Main Methods:

• Designed microfluidic reactors mimicking capillary length scales and shear stresses.
• Employed molecular dynamics simulations to model shear-induced residue accessibility.
• Conducted kinetics experiments to quantify shear-dependent reaction rate changes.

Main Results:

• Shear stress was shown to expose normally buried amino acid residues.
• Reaction rates of these exposed residues increased significantly with shear stress.
• A new microfluidic method was developed for multidimensional cysteine biomarker studies.
• Antibody dissociation of trastuzumab was successfully demonstrated under reducing conditions.

Conclusions:

• Biophysical mimicry, particularly shear stress effects, plays a vital role in biological chemistry.
• The findings have implications for therapeutic antibody stability and efficacy in vivo.
• This work advocates for exploring biophysically mimetic chemistry as a significant research area.