The effect of substrate stiffness on healthy and neurofibromatosis type 1 schwann cell morphology and traction stress generation

Abstract

Neurofibromatosis Type 1 (NF1) is a condition that affects the peripheral system and is manifested in a variety of symptoms. Of those symptoms, this research focuses on learning about the development of the large, soft tumors known as plexiform neurofibromas. For patients with NF1, these tumors can grow anywhere along their peripheral nervous system and carry a ten percent risk of developing into malignant tumors. Currently there is no cure for NF1 and only limited treatments to address specific symptoms. Studies into solid tumor models found that studying the biomechanics of diseased cells aided in understanding disease progression and allowed for targeted treatments. Unfortunately, little is known about the biomechanics of plexiform neurofibromas and what distinguishes them from healthy tissue. This research aims to study the unique biomechanics of plexiform and healthy Schwann cells by analyzing the differences in cell morphology and generated cellular stresses, on substrates of variable stiffness. Varying the stiffness of the microenvironment grants insight into how these cells change through development, different tumorigenic states, or in healthy tissue. This research successfully developed the methods necessary to analyze cells adhered to soft substrates, along with measuring generated cellular traction stresses. The results demonstrate significant differences in cell morphology between the healthy and plexiform Schwann cells for defined cell shapes, cell aspect ratios, and cell area. This research also successfully measured traction stresses generated by these cells. This work is just the beginning of characterizing the biomechanics of NF1 associated cells and leads the way for future mechanobiological studies for NF1.