20 research outputs found
The role of membrane curvature in nanoscale topography-induced intracellular signaling
Over the past decade, there has been growing interest in developing biosensors and devices with nanoscale and vertical topography. Vertical nanostructures induce spontaneous cell engulfment, which enhances the cell–probe coupling efficiency and the sensitivity of biosensors. Although local membranes in contact with the nanostructures are found to be fully fluidic for lipid and membrane protein diffusions, cells appear to actively sense and respond to the surface topography presented by vertical nanostructures. For future development of biodevices, it is important to understand how cells interact with these nanostructures and how their presence modulates cellular function and activities. How cells recognize nanoscale surface topography has been an area of active research for two decades before the recent biosensor works. Extensive studies show that surface topographies in the range of tens to hundreds of nanometers can significantly affect cell functions, behaviors, and ultimately the cell fate. For example, titanium implants having rough surfaces are better for osteoblast attachment and host–implant integration than those with smooth surfaces. At the cellular level, nanoscale surface topography has been shown by a large number of studies to modulate cell attachment, activity, and differentiation. However, a mechanistic understanding of how cells interact and respond to nanoscale topographic features is still lacking. In this Account, we focus on some recent studies that support a new mechanism that local membrane curvature induced by nanoscale topography directly acts as a biochemical signal to induce intracellular signaling, which we refer to as the curvature hypothesis. The curvature hypothesis proposes that some intracellular proteins can recognize membrane curvatures of a certain range at the cell-to-material interface. These proteins then recruit and activate downstream components to modulate cell signaling and behavior. We discuss current technologies allowing the visualization of membrane deformation at the cell membrane-to-substrate interface with nanometer precision and demonstrate that vertical nanostructures induce local curvatures on the plasma membrane. These local curvatures enhance the process of clathrin-mediated endocytosis and affect actin dynamics. We also present evidence that vertical nanostructures can induce significant deformation of the nuclear membrane, which can affect chromatin distribution and gene expression. Finally, we provide a brief perspective on the curvature hypothesis and the challenges and opportunities for the design of nanotopography for manipulating cell behavior.Accepted versio
Dual-Functional Lipid Coating for the Nanopillar-Based Capture of Circulating Tumor Cells with High Purity and Efficiency
Clinical
studies of circulating tumor cells (CTC) have stringent demands for
high capture purity and high capture efficiency. Nanostructured surfaces
have been shown to significantly increase the capture efficiency yet
suffer from low capture purity. Here we introduce a dual-functional
lipid coating on nanostructured surfaces. The lipid coating serves
both as an effective passivation layer that helps prevent nonspecific
cell adhesion and as a functionalized layer for antibody-based specific
cell capture. In addition, the fluidity of lipid bilayers enables
antibody clustering that enhances the cell–surface interaction
for efficient cell capture. As a result, the lipid-coating method
helps promote both the capture efficiency and capture purity of nanostructure-based
CTC capture
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Membrane curvature underlies actin reorganization in response to nanoscale surface topography
Surface topography profoundly influences cell adhesion, differentiation, and stem cell fate control. Numerous studies using a variety of materials demonstrate that nanoscale topographies change the intracellular organization of actin cytoskeleton and therefore a broad range of cellular dynamics in live cells. However, the underlying molecular mechanism is not well understood, leaving why actin cytoskeleton responds to topographical features unexplained and therefore preventing researchers from predicting optimal topographic features for desired cell behavior. Here we demonstrate that topography-induced membrane curvature plays a crucial role in modulating intracellular actin organization. By inducing precisely controlled membrane curvatures using engineered vertical nanostructures as topographies, we find that actin fibers form at the sites of nanostructures in a curvature-dependent manner with an upper limit for the diameter of curvature at ∼400 nm. Nanotopography-induced actin fibers are branched actin nucleated by the Arp2/3 complex and are mediated by a curvature-sensing protein FBP17. Our study reveals that the formation of nanotopography-induced actin fibers drastically reduces the amount of stress fibers and mature focal adhesions to result in the reorganization of actin cytoskeleton in the entire cell. These findings establish the membrane curvature as a key linkage between surface topography and topography-induced cell signaling and behavior
Revealing the Cell–Material Interface with Nanometer Resolution by Focused Ion Beam/Scanning Electron Microscopy
The
interface between cells and nonbiological surfaces regulates
cell attachment, chronic tissue responses, and ultimately the success
of medical implants or biosensors. Clinical and laboratory studies
show that topological features of the surface profoundly influence
cellular responses; for example, titanium surfaces with nano- and
microtopographical structures enhance osteoblast attachment and host–implant
integration as compared to a smooth surface. To understand how cells
and tissues respond to different topographical features, it is of
critical importance to directly visualize the cell–material
interface at the relevant nanometer length scale. Here, we present
a method for <i>in situ</i> examination of the cell-to-material
interface at any desired location, based on focused ion beam milling
and scanning electron microscopy imaging to resolve the cell membrane-to-material
interface with 10 nm resolution. By examining how cell membranes interact
with topographical features such as nanoscale protrusions or invaginations,
we discovered that the cell membrane readily deforms inward and wraps
around protruding structures, but hardly deforms outward to contour
invaginating structures. This asymmetric membrane response (inward <i>vs</i> outward deformation) causes the cleft width between the
cell membrane and the nanostructure surface to vary by more than an
order of magnitude. Our results suggest that surface topology is a
crucial consideration for the development of medical implants or biosensors
whose performances are strongly influenced by the cell-to-material
interface. We anticipate that the method can be used to explore the
direct interaction of cells/tissue with medical devices such as metal
implants in the future