Load Rate and Temperature Dependent Mechanical Properties of the Cortical Neuron and Its Pericellular Layer Measured by Atomic Force Microscopy

Abstract

When studying the mechanical properties of cells by an indentation technique, it is important to take into account the nontrivial pericellular interface (or pericellular "brush") which includes a pericellular coating and corrugation of the pericellular membrane (microvilli and microridges). Here we use atomic force microscopy (AFM) to study the mechanics of cortical neurons taking into account the presence of the above pericellular brush surrounding cell soma. We perform a systematic study of the mechanical properties of both the brush layer and the underlying neuron soma and demonstrate that the brush layer is likely responsible for the low elastic modulus (<1 kPa) typically reported for cortical neurons. When the contribution of the pericellular brush is excluded, the average elastic modulus of the cortical neuron soma is found to be 3-4 times larger than previously reported values measured under similar physiological conditions. We also demonstrate that the underlying soma behaves as a nonviscous elastic material over the indentation rates studied (1-10 μm/s). As a result, it seems that the brush layer is responsible for the previously reported viscoelastic response measured for the neuronal cell body as a whole, within these indentation rates. Due to of the similarities between the macroscopic brain mechanics and the effective modulus of the pericellular brush, we speculate that the pericellular brush layer might play an important role in defining the macroscopic mechanical properties of the brain.

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans

“…Most biophysical studies have focused on structural and biomechanical properties (18)(19)(20)(21). Although chondroitin sulfate proteoglycans are known to have important biochemical roles (14,22), their unusually large size, their ability to be densely aggregated on HA, and their high negative charge should also strongly influence the physical interaction of proteoglycan-rich PCM (and ECM) with molecules (22), cells (23), and particles (24) including drug delivery vehicles, exosomes, and supermolecular aggregates.…”

Biophysical differences between chronic myelogenous leukemic quiescent and proliferating stem/progenitor cells

“…It has to be noted that the speed used in this work is quite ordinary when studying cell mechanics 45 . Furthermore, as was demonstrated for neurons, the mechanics of the cell body is virtually speed independent within 1-10μm/sec 46 (whereas the parameters of the brush do depend on the ramp speed).…”

AFM study shows prominent physical changes in elasticity and pericellular layer in human acute leukemic cells due to inadequate cell–cell communication

“…Because of electrostatic and steric interactions of all biochemical moieties with the pericellular layer, this layer might serve as a protective shell preventing entry of (negatively charged) anticancer drugs into the cell body, or oppositely, the brush molecules can attract and accumulate the positively charged drugs, enhancing its efficacy. This recently was demonstrated for nanoparticles [51, 75]. …”

“…It has to be noted that the speed used in this work is quite ordinary when studying cell mechanics [50]. Furthermore, as was demonstrated for neurons, the mechanics of the cell body is virtually speed independent within 1-10μm/sec [51] (whereas the parameters of the brush do depend on the ramp speed).…”