3 research outputs found
Mechanical Cues for Triggering and Regulating Cellular Movement Selectively at the Single-Cell Level
Cell motility plays important roles in many biophysical
and physiological
processes ranging from in vitro biomechanics, wound healing, to cancer
metastasis. This work introduces a new means to trigger and regulate
motility individually using transient mechanical stimulus applied
to designated cells. Using BV2 microglial cells, our investigations
indicate that motility can be reproducibly and reliably initiated
using mechanical compression of the cells. The location and magnitude
of the applied force impact the movement of the cell. Based on observations
from this investigation and current knowledge of BV2 cellular motility,
new physical insights are revealed into the underlying mechanism of
force-induced single cellular movement. The process involves high
degrees of myosin activation to repair actin cortex breakages induced
by the initial mechanical compression, which leads to focal adhesion
degradation, lamellipodium detachment, and finally,
cell polarization and movement. Modern technology enables accurate
control over force magnitude and location of force delivery, thus
bringing us closer to programming cellular movement at the single-cell
level. This approach is of generic importance to other cell types
beyond BV2 cells and has the intrinsic advantages of being transient,
non-toxic, and non-destructive, thus exhibiting high translational
potentials including mechano-based therapy
Mechanical Cues for Triggering and Regulating Cellular Movement Selectively at the Single-Cell Level
Cell motility plays important roles in many biophysical
and physiological
processes ranging from in vitro biomechanics, wound healing, to cancer
metastasis. This work introduces a new means to trigger and regulate
motility individually using transient mechanical stimulus applied
to designated cells. Using BV2 microglial cells, our investigations
indicate that motility can be reproducibly and reliably initiated
using mechanical compression of the cells. The location and magnitude
of the applied force impact the movement of the cell. Based on observations
from this investigation and current knowledge of BV2 cellular motility,
new physical insights are revealed into the underlying mechanism of
force-induced single cellular movement. The process involves high
degrees of myosin activation to repair actin cortex breakages induced
by the initial mechanical compression, which leads to focal adhesion
degradation, lamellipodium detachment, and finally,
cell polarization and movement. Modern technology enables accurate
control over force magnitude and location of force delivery, thus
bringing us closer to programming cellular movement at the single-cell
level. This approach is of generic importance to other cell types
beyond BV2 cells and has the intrinsic advantages of being transient,
non-toxic, and non-destructive, thus exhibiting high translational
potentials including mechano-based therapy
Engineering Amyloid Fibrils from β‑Solenoid Proteins for Biomaterials Applications
Nature provides numerous examples of self-assembly that can potentially be implemented for materials applications. Considerable attention has been given to one-dimensional cross-β or amyloid structures that can serve as templates for wire growth or strengthen materials such as glue or cement. Here, we demonstrate controlled amyloid self-assembly based on modifications of β-solenoid proteins. They occur naturally in several contexts (e.g., antifreeze proteins, drug resistance proteins) but do not aggregate <i>in vivo</i> due to capping structures or distortions at their ends. Removal of these capping structures and regularization of the ends of the spruce budworm and rye grass antifreeze proteins yield micron length amyloid fibrils with predictable heights, which can be a platform for biomaterial-based self-assembly. The design process, including all-atom molecular dynamics simulations, purification, and self-assembly procedures are described. Fibril formation with the predicted characteristics is supported by evidence from thioflavin-T fluorescence, circular dichroism, dynamic light scattering, and atomic force microscopy. Additionally, we find evidence for lateral assembly of the modified spruce budworm antifreeze fibrils with sufficient incubation time. The kinetics of polymerization are consistent with those for other amyloid formation reactions and are relatively fast due to the preformed nature of the polymerization nucleus