Reality-Based Real-Time Cell Indentation Simulator

Abstract

International audienceTraining simulators that provide realistic visual and haptic feedback during cell indentation tasks are currently inves tigated. Complex cell geometry inherent to biological cells and intricate mechanical properties drive the need for precise mechan ical and numerical modeling to assure accurate cell deformation and force calculations. Advances in alternative finite-element for mulation, such as the mass-tensor approach, have reached a state, where they are applicable to model soft-cell deformation in real time. The geometrical characteristics and the mechanical proper ties of different cells are determined with atomic force microscopy (AFM) indentation. A real-time, haptics-enabled simulator for cell centered indentation has been developed, which utilizes the AFM data (mechanical and geometrical properties of embryonic stem cells) to accurately replicate the indentation task and predict the cell deformation during indentation in real time. This tool can be used as a mechanical marker to characterize the biological state of the cell. The operator is able to feel the change in the stiff ness during cell deformation between fixed and live cells in real time. A comparative study with finite-element simulations using a commercial software and the experimental data demonstrate the effectiveness of the proposed physically based model

Mechanical Phenotyping of Mouse Embryonic Stem Cells: Increase in Stiffness with Differentiation

“…As the cantilever moved further in the z direction and deformed the cell, the final cantilever deflection (d 1 ), and the cantilever movement (z 1 ), were obtained (Pillarisetti et al, 2008). Prior to any experiments, cantilevers were calibrated to determine resonant frequency and spring constant (see Ladjal et al, 2010), since for each particular tip geometry, the stiffness of the cantilever plays a crucial role in determining the elastic modulus of the cell. After conducting several trials, a silicon nitride cantilever with spring constant of 0.06 N/m (Novascan Technologies, Inc., Ames, IA) was chosen for indenting live ESCs, whereas a relatively stiffer silicon cantilever (k * 2 N/ m, Novascan Technologies, Inc.) was chosen for indenting fixed ESCs.…”

“…Specifically, at the beginning of each experiment, the probe tip was touched to the dish surface near a cell and the spring constant determined through the software (Ladjal et al, 2010). The spring constant was computed by the thermal noise method (Hutter and Bechhoefer, 1993), which takes into consideration the sensitivity factor of the cantilever.…”

“…However, the indentation range depends on the cell height, which was calculated from force-displacement curves obtained on a hard surface near the cell and on the cell surface. The mESC heights were approximately in the range of 7-17 mm (Ladjal et al, 2010). The cell indentation range was chosen to be 2-2.5 mm.…”

“…The cell indentation range was chosen to be 2-2.5 mm. As the indentation range becomes a significant fraction of the cell height it is necessary to develop an appropriate contact model that can account for the observed force-indentation data (Ladjal et al, 2010). The cell was deformed by using the ''indentation trigger'' (custom made by Asylum Research) based on the equation…”

Micro-to-Nano Biomechanical Modeling for Assisted Biological Cell Injection

“…The objective of this paper is to develop and implement a biomechanical finite element approach within a virtual environment dedicated to real-time cell injection to facilitate training of ICSI operations. These models include the topological information of the living cells (shape and dimensions), and the biological structure (cytoplasm layers, cytoskeletons and nucleus) [6], [13], [14].…”