Mechanoprobe fabrication and development for mechanobiology

Mounting evidence supports the notion that mechanical cues are one of the key regulators of cell functions driving many important biological phenomena like development, morphogenesis, differentiation, and disease. As a result, further progress in full understanding of the role of mechanics in biology requires the technologies to quantify tractions and stiffness as two essential parameters in physiology and pathology. Despite the extensive efforts in recent decades, it has been yet extremely challenging to quantify both traction and stiffness in vivo in a living animal. To address this challenge, we first introduce the fluorescent nanoparticle-labeled, mono-disperse biocompatible, elastic round microgel (ERMG) of Arg-Gly-Asp conjugated alginate hydrogels as a passive force sensor to quantify compressive, tensile stresses, and shear stresses in cancer cell layer, and cancer cell colony. The exerted force by surrounding cells deformed the soft ERMG (1.4 kPa Young’s modulus), and the deformation was captured using digital volume correlation comparing the stressed and stress-free microgel. Subsequently, the strain, stress, and applied traction were calculated from the cell-induced deformation of the microgel. We further extend our approach by developing a novel mechanomicrorobot with controllable functionality via magnetic fields to measure cellular tractions and the mechanical properties of the microenvironment in live 3D tissue in the same location in vivo. The mechanomicrorobot is the result of integrating two ideas: elastic round microgel (ERMG) and magnetic twisting cytometry (MTC) by fabrication of biocompatible ferromagnetic micro-structure and its encapsulation in photodegradable elastic round microgel. In this approach, the initially stiff mechanomicrorobot is actuated by an oscillating twisting magnetic field to probe the microenvironment by its rigid rotation. Following the stiffness measurement, the mechanomicrorobot can be dynamically softened by controlling the UV exposure time to tune its modulus and probe a wide range of 3D tractions generated by a biological sample. Using this novel approach, we demonstrate that mechanomicrorobot probe can reveal distinct modulus and tractions in tumor cell colonies. Collectively, these results strongly suggest that ERMG and mechanomicrorobot can be used in a broad range of in vivo studies in mechanobiology and provide future insights into the role of mechanical factors in tumor progression and organogenesis during embryonic development.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Mechanical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Mohagheghian, Erfan

Contributors dc:contributor

• Wang, Ning
• Ewoldt, Randy
• Johnson, Amy Wagoner
• Underhill, Gregory

• Mechanobiology
• Cell traction
• Cell and Tissue Stiffness

Statement dc:rights

• Copyright 2022 Erfan Mohagheghian

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/115946

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F115946