Quantification of Magnetically Induced Changes in ECM Local Apparent Stiffness

Abstract

The stiffness of the extracellular matrix (ECM) is known to influence cell behavior. The ability to manipulate the stiffness of ECM has important implications in understanding how cells interact mechanically with their microenvironment. This article describes an approach to manipulating the stiffness ECM, whereby magnetic beads are embedded in the ECM through bioconjugation between the streptavidin-coated beads and the collagen fibers and then manipulated by an external magnetic field. It also reports both analytical results (obtained by formal modeling and numerical simulation) and statistically meaningful experimental results (obtained by atomic force microscopy) that demonstrate the effectiveness of this approach. These results clearly suggest the possibility of creating desired stiffness gradients in ECM in vitro to influence cell behavior.

Three-Dimensional Characterization of Mechanical Interactions between Endothelial Cells and Extracellular Matrix during Angiogenic Sprouting

“…For gelation, the devices were placed in an incubator at 37 °C and 5% CO 2 . The local stiffness of polymerized gel with a similar concentration of collagen to that used in these experiments has been tested to 33.59 Pa in atomic force microscopy indentation experiments 45 . It is important to note that for soft biological material, the stiffness at the macro-scale level may be several thousands of times higher than that at the micro-scale level 46 .…”

An Electromagnetic System for Inducing a Localized Force Gradient in an ECM and Its Influence on HMVEC Sprouting

“…The magnetic technique applied to sECM appears to mimic durotaxis, which is a form of cell migration guided by matrix stiffness gradients. Several works [20][21][22] have already shown that by embedding magnetic particles in ECM and by applying an external magnetic field, the stiffness of the ECM can be mechanically manipulated. While these works provided useful insight on the mechanical properties of the ECM, how mechanical stimulus (in the form of a force gradient) directly affects the cell behaviors still remains preliminary and several issues need to be clarified.…”

“…Recent results [20][21][22] have demonstrated that ECM stiffness can be altered by mechanically manipulating the deformability of the collagen fibers in the ECM through magnetic manipulation. The proposed approach works by embedding magnetic particles in the ECM through bioconjugation with the collagen fibers and then employing a magnetic field gradient to exert forces on the particles.…”

“…This renders the system unsuitable for investigating the responses of selected sprouts in the device to the applied stimulus without affecting the rest of the sprouts. The aim of this current work was to apply the same approach as reported in our earlier work [20][21][22] to mechanically manipulate the ECM in order to demonstrate the effect of such localized manipulation on in vitro angiogenic sprouting of HMVECs at a phenomenological level.…”

“…In the work reported in Chen et al 23 and Herath et al, 24 a magnetomicrofluidic system (based on the approach of Herath and coworkers 20–22 ) was developed to study the regulation of the ECM stiffness gradient on human microvascular endothelial cell (HMVEC) sprouting. The system uses cuboid permanent magnets (whose magnetic field spreads widely) to induce static forces at the sites in the ECM occupied by the magnetic particles.…”