Magneto-mechanical action of multimodal field configurations on magnetic nanoparticle environments

Highlights

• Device producing different magnetic fields with respect to magnitude and frequency.

• Static, alternating, rotating magnetic fields experimentally, numerically evaluated.

• Force magnitudes calculated based on MNPs physical properties and field gradients.

• An easy-to-use, versatile device for study of mechanical forces exerted on cells.

Abstract

The generation of mechanical forces via magnetic fields, the so called magneto-mechanical effect, is a powerful manipulation tool of magnetic nanoparticles inside variable environments. The combination of alternating, static or rotating magnetic field configurations with magnetic nanoparticles allows transformation of electromagnetic to mechanical energy. Such an option renders magnetic nanoparticles, useful in biomedical research, as it is possible to functionalize them to specifically bind to malignant cell membranes and incur cell damages by exerting magneto-mechanical stresses. In order to produce these multimodal fields, a novel magneto-mechanical device was designed, manufactured and thoroughly characterized in terms of field parameters and magnetic nanoparticle properties. It consists of a rotating turntable, on which different magnetic field configurations were established by orderly arrangements of commercial Nd-Fe-B permanent magnets. For each configuration, the field gradients and mechanical forces acting on different magnetic nanoparticles, in terms of size and material, were calculated numerically by using COMSOL 3.5a Multiphysics. Such a device may be further implemented, as a versatile magnetic force performer, on cellular environments, where the magnetic nanoparticles, following external magnetic field variations, may ignite cellular processes.

Introduction

The manipulation of magnetic nanoparticles (MNPs) by using magnetic fields of variable amplitude and frequency is a topic of great interest in a wide range of research and technological areas [1], [2], [3]. Usually, MNPs, possessing tunable magnetizations, are dispersed in a non-magnetic liquid carrier, resulting in a colloidal suspension often referred to as “ferrofluid”. Depending on packing fraction and magnetic coupling, the application of an external magnetic field may drive their assembly towards highly ordered structures, such as clusters [4], chains [5], or large crystalline lattices [6] outlining the additional transfer, rotational or vibrational degrees of freedom in overall MNPs performance. The most striking example of an effective magnetic field force acting upon the MNPs, driving them to regions of higher magnetic flux, is the MNPs separation from a solution achieved by high magnetic field gradients [7]. This mechanism, which is known as magneto-mechanical effect, beneficially contributes to the final force outcome, jointly with the electrostatic, van der Waals forces and the magnetic dipole–dipole interaction and may lead to a diverse series of cellular processes, if particles are attached to cell membranes or even endocytosed [8].

In general, mechanical stress applied to the cell membrane, cytoskeleton, or organelles plays an important role in crucial intracellular processes [9], [10]. Moreover, several biophysical and/or biochemical effects may originate when biological systems are simultaneously exposed to static or time-varying magnetic fields and other forms of energy dissipation such as light or radiation [11]. Several studies, report on cell damages when exposed to alternating magnetic fields even without a perceptible raise in temperature [12], [13], [14], [15], [16].

Some representative examples of biomedical applicability of magneto-mechanical stress induced by MNPs include the suppression of the tumor growth due to mechanical effects [17], cell levitation in a paramagnetic solution [18], magnetically driven endocytosis triggering in prostate cancer cells [19], stem cell networking on micro-magnet arrays [20], swelling and apoptosis of THP-1 monocytic leukemia cells [21] or even a reprogramming pathway of a cell into an embryonic state [22].

Current research in the area of diagnostic tests and experimental therapies for malignant regions often requires the utilization of ferrofluids because they can be used (a) to deliver drugs to a specific target tissue, (b) to absorb toxins and remove them from the body, or (c) to destroy cancer cells mechanically through the aforementioned forces, depending on the nanoparticle based platform used [23]. Also, the evaluation of the effectiveness of a functionalized magnetic force to aid MNPs in crossing the blood-brain barrier has been recently investigated [24].

In this paper, a home-made, facile, multimodal, magnetic field generator, with tunable amplitude (0–200 mT) and frequency (0–16 Hz) is proposed as a performer exerting forces on MNPs. Despite their phenomenologically low frequencies, such field modes, may intrigue specific cell responses. In particular, El Haj and Dobson have engineered a special magnetic bioreactor in which an alternating magnetic field with an amplitude of up to 120 mT, gradient 11 T/m and frequencies from 0 to 1 Hz can be generated by the mechanically moving sets of permanent magnets [25], [26]. Also in [27] a vibration frequency of 4 Hz, achieved pronounced effects of vibrations, on the mesenchymal stem cell cultures. As reported in [28] low frequency (5 Hz) magnetomechanical stimulation of cardiac cells seeded in magnetically responsive scaffolds can promote cells’ organization and subsequent myocardial tissue regeneration through the activation of the AKT (also known as protein kinase B, a serine/threonine-specific protein kinase) pathway. In another work [29] magneto-mechanical stimulation was applied to human bone marrow stromal cells (hBMSC) labeled with 250 nm magnetic beads via 1 Hz alternating magnetic field pulses. The designated static, alternating and rotating magnetic fields are experimentally quantified and numerically evaluated. Cell types, adsorb in a variable extent MNPs, with respect to their gene expression profiles and particle properties (i.e. MNP and cell sizes, types and morphologies) and eventually are expected to respond differently to external magnetic fields. Thus, the estimation of the force per cell magnitude is cell and MNP -specific and is statistically estimated over the number of MNPs either attached or even internalized at a cellular level [30]. On the other hand, the force per particle, which is the factor summed up to provide ultimate mechanical force per cell, is solely dependent on the applied magnetic field parameters and specific MNPs collective features and may provide the adequate reference input data for subsequent in vitro studies on different cell types.