Life on Magnets: Stem Cell Networking on Micro-Magnet Arrays

Abstract

Interactions between a micro-magnet array and living cells may guide the establishment of cell networks due to the cellular response to a magnetic field. To manipulate mesenchymal stem cells free of magnetic nanoparticles by a high magnetic field gradient, we used high quality micro-patterned NdFeB films around which the stray field’s value and direction drastically change across the cell body. Such micro-magnet arrays coated with parylene produce high magnetic field gradients that affect the cells in two main ways: i) causing cell migration and adherence to a covered magnetic surface and ii) elongating the cells in the directions parallel to the edges of the micro-magnet. To explain these effects, three putative mechanisms that incorporate both physical and biological factors influencing the cells are suggested. It is shown that the static high magnetic field gradient generated by the micro-magnet arrays are capable of assisting cell migration to those areas with the strongest magnetic field gradient, thereby allowing the build up of tunable interconnected stem cell networks, which is an elegant route for tissue engineering and regenerative medicine.

How a High-Gradient Magnetic Field Could Affect Cell Life

“…As seen from Figs 1 and 2, there are several areas with the highest magnetic gradient. Thus, in the experiments46, driven by magnetic gradient forces (Equation 2), cell migration was observed towards the areas with the strongest magnetic field gradient, thereby allowing the buildup of tunable, interconnected, stem cell networks.…”

“…2; one can compare these forces with the gravitational force density, f g  =  ρg  = 10 4  Nm −3 (where ρ is the density of water and g is the acceleration of gravity). Assuming Δχ to be 10–20%46 of the diamagnetic susceptibility of water (χ w  = −9 ⋅10 −6 in SI), B = 1 T and |∇B| = 10 6  Tm −1 , from Eq. 2, we obtain the magnetic force density f  = (0.7–1.4) · 10 6  Nm −3 , which yields f  ≫  f g .…”

“…It was recently demonstrated in ref. 46 that micromagnet arrays (with lateral size of 30–50 μm and the same neighboring distances) coated with parylene produce high magnetic field gradients (up to 10 6  Tm −1 ) that affect cell behavior in two main ways: i) causing cell migration and adherence to a covered magnetic surface and ii) elongating the cells in the direction parallel to the edges of the micromagnet. The results of the calculations of the magnetic field and gradient distributions above four micromagnets are shown in Figs 1 and 2.…”

“…Recent studies indicate the crucial influence of external mechanical and magnetic forces on the cell shape, function and fate through physical interactions with the cytoskeleton network464956.…”

“…In HGMFs with magnetic gradient of approximately |∇B| ≈ 10 9  Tm −1 , a cell response (change of the resting membrane) is expected within a second. Migration and adhesion of stem cells to the edges of micromagnets (at the edge |∇B| ≈ 10 6  Tm −1 ) with subsequent cytoskeleton remodeling and changes of cell shape were observed during the first 4 hours after cell culture deposition on the magnetic system46. During the following 3 days, the cells migrated and occupied the tops of the micromagnets, creating patterns that reflect the spatial distribution of magnetic gradient forces generated by micromagnet arrays46.…”