Force-Mediating Magnetic Nanoparticles to Engineer Neuronal Cell Function

Abstract

Cellular processes like membrane deformation, cell migration, and transport of organelles are sensitive to mechanical forces. Technically, these cellular processes can be manipulated through operating forces at a spatial precision in the range of nanometers up to a few micrometers through chaperoning force-mediating nanoparticles in electrical, magnetic, or optical field gradients. But which force-mediating tool is more suitable to manipulate cell migration, and which, to manipulate cell signaling? We review here the differences in forces sensation to control and engineer cellular processes inside and outside the cell, with a special focus on neuronal cells. In addition, we discuss technical details and limitations of different force-mediating approaches and highlight recent advancements of nanomagnetics in cell organization, communication, signaling, and intracellular trafficking. Finally, we give suggestions about how force-mediating nanoparticles can be used to our advantage in next-generation neurotherapeutic devices.

Parallelized Manipulation of Adherent Living Cells by Magnetic Nanoparticles-Mediated Forces

“…On the other hand, the non-specific mechanical approach constitutes a much more advanced magnetic mode for remotely guiding cell motility and nerve growth, albeit not as specific as the engineered MNPs. As a matter of fact, MNPs have long been used to exert tensile forces on cells, tissue or substrates, and it is well established that physical forces play a key role in cell polarity, migration and in shaping neuronal structure [ 14 ]. During migration, the coordinated assembly of multiple actin filaments produces protrusive forces that drive the extension of the plasma membrane (protrusions) at the cell leading edge [ 15 ].…”

Parallelized manipulation of adherent living cells by magnetic nanoparticles-mediated forces

“…On the other hand, the non-specific mechanical approach constitutes a much more advanced magnetic mode for remotely guiding cell motility and nerve growth, albeit not as specific as the engineered MNPs. As a matter of fact, MNPs have long been used to exert tensile forces on cells, tissue or substrate, and it is well established that physical forces play a key role in cell polarity, migration and in shaping neuronal structure (Gahl and Kunze 2018). During migration, the coordinated assembly of multiple actin filaments produces protrusive forces that drive the extension of the plasma membrane (protrusions) at the cell leading edge (Svitkina 2018).…”

Manipulation of Axonal Outgrowth via Exogenous Low Forces

“…They were recently used to direct neuronal cell growth, but also to stretch neurons [66,78,79]. Generally, MNPs are no larger than 100 nm, are primarily composed of iron oxide, are coated with organic or inorganic elements, and may be conjugated with functional groups [53]. The size of MNPs facilitates internalization in neurons, allowing inward stretching on neurites [78,87].…”

“…As the axon has machinery to sense and generate forces, it also responds to the application of exogenous forces. Neurons are mechanosensitive over three distinct ranges of force magnitude (for a review, see [53,54]); however, in this review, we will focus on forces whose magnitude is similar to those generated in vivo (<2 nN) [7,55]. Nevertheless, through these exogenous low forces, it is possible to influence every phase of neuron development ( Figure 2).…”