Sickle cell vasoocclusion and rescue in a microfluidic device.

Area of Science:

• Biophysics
• Hematology
• Translational Medicine

Background:

• Sickle cell disease (SCD) pathophysiology involves complex multiscale processes from molecular hemoglobin polymerization to organismal vaso-occlusion.
• Understanding the dynamics of these processes is crucial for developing effective SCD treatments.

Purpose of the Study:

• To develop and utilize a microfluidic model to evoke, control, and inhibit vaso-occlusive events in SCD.
• To quantify the phase space for jamming onset and dissolution, and investigate factors contributing to occlusion heterogeneity.

Main Methods:

• Employing a microfluidic environment integrating geometric, physical, chemical, and biological approaches.
• Analyzing oxygen-dependent sickle hemoglobin polymerization and melting dynamics.
• Investigating the effects of polymerization inhibitors and red blood cell exchange on occlusion.

Main Results:

• Demonstrated that oxygen-dependent sickle hemoglobin polymerization and melting are sufficient to recreate and rescue jamming events.
• Identified slow collective jamming of flowing, deformable cells as a source of occlusion heterogeneity.
• Quantified the impact of small-molecule inhibitors and red blood cell exchange on the occlusion dynamics.

Conclusions:

• The study provides a quantitative understanding of rate-limiting processes in SCD vaso-occlusion.
• The microfluidic platform serves as a potential tool for optimizing SCD treatments and identifying new therapeutic strategies.
• This research integrates molecular, cellular, and tissue-level dynamics to address SCD pathophysiology.