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The formation of neuron networks is a complex phenomenon of fundamental importance for understanding the development of the nervous system, and for creating novel bioinspired materials for tissue engineering and neuronal repair. The basic process underlying the network formation is axonal growth, a process involving the extension of axons from the cell body towards target neurons. Axonal growth is guided by environmental stimuli that include intercellular interactions, biochemical cues, and the mechanical and geometrical features of the growth substrate. The dynamics of the growing axon and its biomechanical interactions with the growing substrate remains poorly understood. In this paper, we develop a model of axonal motility which incorporates mechanical interactions between the axon and the growth substrate. We combine experimental data with theoretical analysis to measure the parameters that describe axonal growth on surfaces with micropatterned periodic geometrical features: diffusion (cell motility) coefficients, speed and angular distributions, and axon bending rigidities. Experiments performed on neurons treated Taxol (inhibitor of microtubule dynamics) and Blebbistatin (disruptor of actin filaments) show that the dynamics of the cytoskeleton plays a critical role in the axon steering mechanism. Our results demonstrate that axons follow geometrical patterns through a contact-guidance mechanism, in which high-curvature geometrical features impart high traction forces to the growth cone. These results have important implications for our fundamental understanding of axonal growth as well as for bioengineering novel substrates that promote neuronal growth and nerve repair.

Neurofilaments(NFs) are the most abundant intermediate filaments that make up the inner volume of axon, with possible phosphorylation on their side arms, and their slow axonal transport by molecular motors along microtubule tracks in a “stop-and-go” manner with rapid, intermittent and bidirectional motion. The kinetics of NFs and morphology of axon are dramatically different between myelinate internode and unmyelinated node of Ranvier. The NFs in the node transport as 7.6 times faster as in the internode, and the distribution of NFs population in the internode is 7.6 folds as much as in the node of Ranvier. We hypothesize that the phosphorylation of NFs could reduce the on-track rate and slow down their transport velocity in the internode. By modifying the ‘6-state’ model with (a) an extra phosphorylation kinetics to each six state and (b) construction a new ‘8-state’ model in which NFs at off-track can be phosphorylated and have smaller on-track rate, our model and simulation demonstrate that the phosphorylation-induced decrease of on-track rate could slow down the NFs average velocity and increase the axonal caliber. The degree of phosphorylation may indicate the extent of velocity reduction. The Continuity equation used in our paper predicts that the ratio of NFs population is inverse proportional to the ratios of average velocity of NFs between node of Ranvier and internode. We speculate that the myelination of axon could increase the level of phosphorylation of NF side arms, and decrease the possibility of NFs to get on-track of microtubules, therefore slow down their transport velocity. In summary, our work provides a potential mechanism for understanding the phosphorylation kinetics of NFs in regulating their transport and morphology of axon in myelinated axons, and the different kinetics of NFs between node and internode.

Organelle selective imaging can reveal structural and functional characters of cells undergoing external stimuli, and is considered critical in revealing biological fundamentals, designing targeted delivery system, and screening potential drugs and therapeutics. This paper describes the nucleoli targeting ability of nanoscale carbon dots (including nanodiamond) that are hydrothermally made with controlled surface charges. The surface charges of carbon dots are controlled in the range of -17.9 to -2.84 mV by changing the molar ratio of two precursors, citric acid (CA) and ethylenediamine (EDA). All carbon dots samples show strong fluorescence under wide excitation wavelength, and samples with both negative and positve charges show strong fluorescent contrast from stained nucleoli. The nucleoli selective imaging of live cell has been confirmed with Hoechst staining and nucleoli specific staining (SYTO RNA-select green), and is explained as surface charge heterogeneity on carbon dots. Carbon dots with both negative and positive charges have better ability to penetrate cell and nucleus membranes, and the charge heterogeneity helps carbon dots to bind preferentially to nucleoli, where the electrostatic environment is favored.

Endosseous titanium (Ti) implant failure due to poor biocompatibility of implant surface remains a major problem for osseointegration. Improving the topography of Ti surface may enhance osseointegration, however, the mechanism remains unknown. To investigate the effect of modified Ti surface on osteogenesis, we loaded rapamycin (RA) onto nano-hydroxyapatite (HAp) coated Ti surface which was acid-etched, alkali-heated and HAp coated sequentially. Sodium hyaluronate (SH) was employed as an intermediate layer for the load of RA, and a steady release rate of RA was maintained. Cell vitality of MC3T3-E1 was assessed by MTT. Osteogenesis of MC3T3-E1 on this modified Ti surface was evaluated by alkaline phosphatase (ALP) activity, mineralization and related osteogenesis genes osteocalcin (OCN), osteopontin (OPN), Collagen-I and Runx2. The result revealed that RA/SH-loaded nano-HAp Ti surface was innocent for cell vitality and even more beneficial for cell osteogenesis in vitro. Furthermore, osteogenesis of MC3T3-E1 showed significant association with the mammalian target of rapamycin (mTOR) phosphorylation by RA, which required further study about the mechanism. The approach to this modified Ti surface presented in this paper has high research value for the development of Ti-based implant.

Learning based on networks of real neurons, and by extension biologically inspired models of neural networks, has yet to find general learning rules leading to widespread applications. In this paper, we argue for the existence of a principle allowing to steer the dynamics of a biologically inspired neural network. Using carefully timed external stimulation, the network can be driven towards a desired dynamical state. We term this principle "Learning by Stimulation Avoidance" (LSA). We demonstrate through simulation that the minimal sufficient conditions leading to LSA in artificial networks are also sufficient to reproduce learning results similar to those obtained in biological neurons by Shahaf and Marom [1]. We examine the mechanism's basic dynamics in a reduced network, and demonstrate how it scales up to a network of 100 neurons. We show that LSA has a higher explanatory power than existing hypotheses about the response of biological neural networks to external simulation, and can be used as a learning rule for an embodied application: learning of wall avoidance by a simulated robot. The surge in popularity of artificial neural networks is mostly directed to disembodied models of neurons with biologically irrelevant dynamics: to the authors' knowledge, this is the first work demonstrating sensory-motor learning with random spiking networks through pure Hebbian learning., 17 pages, 11 figures

This paper reports the damaging effects of magnetic iron-oxide nanoparticles (MNP) on magnetically labeled cancer cells when subjected to oscillating gradients in a strong external magnetic field. Human breast cancer MDA-MB-231 cells were labeled with MNP, placed in the high magnetic field, and subjected to oscillating gradients generated by an imaging gradient system of a 9.4T preclinical MRI system. Changes in cell morphology and a decrease in cell viability were detected in cells treated with oscillating gradients. The cytotoxicity was determined qualitatively and quantitatively by microscopic imaging and cell viability assays. An approximately 26.6% reduction in cell viability was detected in magnetically labeled cells subjected to the combined effect of a static magnetic field and oscillating gradients. No reduction in cell viability was observed in unlabeled cells subjected to gradients, or in MNP-labeled cells in the static magnetic field. As no increase in local temperature was observed, the cell damage was not a result of hyperthermia. Currently, we consider the coherent motion of internalized and aggregated nanoparticles that produce mechanical moments as a potential mechanism of cell destruction. The formation and dynamics of the intracellular aggregates of nanoparticles were visualized by optical and transmission electron microscopy (TEM). The images revealed a rapid formation of elongated MNP aggregates in the cells, which were aligned with the external magnetic field. This strategy provides a new way to eradicate a specific population of MNP-labeled cells, potentially with magnetic resonance imaging guidance using standard MRI equipment, with minimal side effects for the host.