Fibroblast Migration in 3D is Controlled by Haptotaxis in a Non-muscle Myosin II-Dependent Manner

Abstract

Cell migration in 3D is a key process in many physiological and pathological processes. Although valuable knowledge has been accumulated through analysis of various 2D models, some of these insights are not directly applicable to migration in 3D. In this study, we have confined biomimetic hydrogels within microfluidic platforms in the presence of a chemoattractant (platelet-derived growth factor-BB). We have characterized the migratory responses of human fibroblasts within them, particularly focusing on the role of non-muscle myosin II. Our results indicate a prominent role for myosin II in the integration of chemotactic and haptotactic migratory responses of fibroblasts in 3D confined environments.Electronic supplementary materialThe online version of this article (doi:10.1007/s10439-015-1343-2) contains supplementary material, which is available to authorized users.

Engineering the cellular mechanical microenvironment – from bulk mechanics to the nanoscale

“…The distribution of adhesion ligands also regulates cell polarisation and migration through haptotaxis, the guided migration of cells following a gradient of surface-bound cues and a fundamental process in 3D migration (McCarthy et al, 1983;Moreno-Arotzena et al, 2015). For this reason, techniques that enable precise control over the pattern and concentration of adhesion ligands are a useful platform to research haptotaxis.…”

A Workbench for Biomedical Applications Based on Image Analysis

“…displacement, strain or stress) through Finite Element Analysis (FEA). In fact, it has been successfully used so far to analyze and quantify chemotaxis, migratory patterns depending on mechanical stimuli and sprouting dynamics for different growth factors [3,5,6]. Offering these complete processing to the research community as a commercial online service would be of great interest for many laboratories that need to perform complex analyses and do not have the time, the experience or the resources to use other available tools.…”

“…Some examples of already built-in applications (A) Actin flow velocity mapping at the lamellipodium[2]. (B) Automated cell tracking in 2D[3,4] (C) TFM reconstruction showing 3D extracellular matrix displacements around a cell. (D) Sprout detection in 2D[5].…”

Review on experiment-based two- and three-dimensional models for wound healing

“…For example, Moreno-Arotzena et al [10] have observed that fibroblast migration in three-dimensional hydrogels is controlled by haptotaxis with a key role for myosin II; haptotaxis is migration up a biochemical gradient of adhesion. Similarly, Ladoux & Nicholas [11] have shown that fibroblasts under specific conditions preferentially migrate towards stiffer regions of the substrate, in a process known as durotaxis.…”

“…Cell deformation models were developed based on PDEs, such as by Marth & Voigt [64], who use a phase-field approach to simulate cell motility under the influence of external signals, or by Madzvamuse & George [65], who use a moving mesh approach in a viscoelastic setting to model cell migration and deformation. Here, also the work by Barreto et al [10,66,67] should be mentioned where a structural finite-element method is applied to model cell mechanics, and in particular with respect to environmental variations. These elegant approaches model cell deformation and migration very well, and are based on sound physical principles; however, the computational approach is relatively expensive.…”