Can Cai will defend his dissertation!

Can Cai will defend his PhD dissertation on Wednesday, July 8, 2026, at 1:30 PM, in ZSR Library 204.

Please see the attached flyer.

All are invited.  

Multiscale Quantification of Fibrin Fibers: Standardization, Structure Scaling, and Formation Models

Fibrin forms the structural scaffold of blood clots, and its micro- and nanoscale architecture influences clot mechanical properties, permeability, susceptibility to fibrinolysis, and disease-related behavior. However, quantitative analysis of fibrin structure remains limited by artifacts introduced during scanning electron microscopy preparation and by an incomplete understanding of how fibrinogen concentration, thrombin concentration, and polymerization dynamics regulate network architecture.

This dissertation develops reproducible, artifact-aware microscopy approaches to quantify fibrin structure and investigate fibrin assembly across multiple length scales. A standardized scanning electron microscopy preparation protocol for plasma fibrin clots was validated across eight laboratories worldwide, reducing interlaboratory variability in fiber diameter measurements to 7%. The effects of conductive coating and substrate preparation were then examined, showing that sputter coating systematically increases apparent fiber diameter. To minimize this bias, indium tin oxide-coated glass was introduced as a coating-free platform for low-voltage scanning electron microscopy imaging of fibrin clots.

Using standardized scanning electron microscopy and confocal fluorescence microscopy, this work defines how fibrinogen and thrombin regulate fibrin network architecture in both purified fibrinogen and plasma clot systems. Thrombin primarily controlled the kinetic length scale of fiber growth by shortening branch-to-branch segment length and modestly decreasing fiber diameter, whereas fibrinogen primarily controlled network space filling by increasing fiber density and decreasing pore size. Time-resolved atomic force microscopy and scanning electron microscopy revealed a heterogeneous early assembly process. In more dilute regions, early fibrin assemblies gradually merged and aligned into straighter fiber-like structures, whereas locally dense regions exhibited more rapid clustering and network formation.

Together, this dissertation establishes robust methods for quantitative fibrin ultrastructure analysis, introduces indium tin oxide-coated glass as a coating-free imaging platform, and provides new mechanistic insight into how fibrin networks form, organize, and mature.