Cinemechanometry (CMM): A Method to Determine the Forces that Drive Morphogenetic Movements from Time-Lapse Images

Abstract

Although cell-level mechanical forces are crucial to tissue self-organization in contexts ranging from embryo development to cancer metastases to regenerative engineering, the absence of methods to map them over time has been a major obstacle to new understanding. Here, we present a technique for constructing detailed, dynamic maps of the forces driving morphogenetic events from time-lapse images. Forces in the cell are considered to be separable into unknown active driving forces and known passive forces, where actomyosin systems and microtubules contribute primarily to the first group and intermediate filaments and cytoplasm to the latter. A finite-element procedure is used to estimate the field of forces that must be applied to the passive components to produce their observed incremental deformations. This field is assumed to be generated by active forces resolved along user-defined line segments whose location, often along cell edges, is informed by the underlying biology. The magnitudes and signs of these forces are determined by a mathematical inverse method. The efficacy of the approach is demonstrated using noisy synthetic data from a cross section of a generic invagination and from a planar aggregate that involves two cell types, edge forces that vary with time and a neighbor change.

Video force microscopy reveals the mechanics of ventral furrow invagination in Drosophila

“…Further details of the calculations are given in SI Text and in ref. 11. To determine the active forces acting along each region boundary, matrix equations relating edge forces and intracellular pressures to nodal forces were written.…”

“…The method presented here, which might also be called cinemechanometry (CMM) (11), is fundamentally different from typical computational models. In those models, the researcher uses rational techniques to estimate the forces at work in the system and fine-tunes them so as to make the model output match the experimentally observed motions as closely as possible (4,5), a process that can be quite tedious.…”

Micromechanical regulation in cardiac myocytes and fibroblasts: implications for tissue remodeling

“…These approaches (sometimes referred to as digital image correlation or videomicroscopy analysis) rely on the software-assisted correlation of captured images to track changes in position of visible cell morphology [26]. Cell displacement data can then be paired with the deformation of the culture surface to evaluate both the transfer of forces and the viscoelastic losses at cell-substrate interfaces [49, 80].…”

Estimating intercellular surface tension by laser-induced cell fusion

“…However, the problem is that the relevant viscosity is hard to measure experimentally. This is particularly true for effective viscosity of the whole cell, a quantity that rules all aspects of cell movements [13,14]. Several researchers have assumed that the effective viscosity is equal to the cytoplasmic viscosity [9,11,12].…”