Lévy-like movement patterns of metastatic cancer cells revealed in microfabricated systems and implicated in vivo.

Metastatic cancer cells differ from their non-metastatic counterparts not only in terms of molecular composition and genetics, but also by the very strategy they employ for locomotion. Here, we analyzed large-scale statistics for cells migrating on linear microtracks to show that metastatic cancer cells follow a qualitatively different movement strategy than their non-invasive counterparts. The trajectories of metastatic cells display clusters of small steps that are interspersed with long "flights".

Mechanochemical activation and patterning of an adhesive surface toward nanoparticle deposition.

Mechanical pulling of adhesive tape creates radicals on the tape's surface. These radicals are capable of reducing metal salts to the corresponding metal nanoparticles. In this way, the mechanically activated tape can be decorated with various types of nanoparticles, including Au, Ag, Pd, or Cu.

Microfabricated Systems and Assays for Studying the Cytoskeletal Organization, Micromechanics, and Motility Patterns of Cancerous Cells.

Cell motions are driven by coordinated actions of the intracellular cytoskeleton - actin, microtubules (MTs) and substrate/focal adhesions (FAs). This coordination is altered in metastatic cancer cells resulting in deregulated and increased cellular motility. Microfabrication tools, including photolithography, micromolding, microcontact printing, wet stamping and microfluidic devices have emerged as a powerful set of experimental tools with which to probe and define the differences in cytoskeleton organization/dynamics and cell motility patterns in non-metastatic and metastatic cancer cells.

Motility efficiency and spatiotemporal synchronization in non-metastatic vs. metastatic breast cancer cells.

Metastatic breast cancer cells move not only more rapidly and persistently than their non-metastatic variants but in doing so use the mechanical work of the cytoskeleton more efficiently. The efficiency of the cell motions is defined for entire cells (rather than parts of the cell membrane) and is related to the work expended in forming membrane protrusions and retractions. This work, in turn, is estimated by integrating the protruded and retracted areas along the entire cell perimeter and is standardized with respect to the net translocation of the cell.

Controlled pH stability and adjustable cellular uptake of mixed-charge nanoparticles.

Nanoparticles functionalized with mixed self-assembled monolayers (m-SAMs) comprising positively and negatively charged thiols are stable at both low and high pH but precipitate sharply at the pH where the charges on the particle are balanced (pH(prec)). By adjusting the proportion of the positively and negatively charged ligands in the m-SAM or changing particle size, pH(prec) can be varied flexibly between ~4 and ~7. In addition, changes in the SAMs' composition and particles' net charge translate into different degrees of cellular uptake.

Microtubule guidance tested through controlled cell geometry.

In moving cells dynamic microtubules (MTs) target and disassemble substrate adhesion sites (focal adhesions; FAs) in a process that enables the cell to detach from the substrate and propel itself forward. The short-range interactions between FAs and MT plus ends have been observed in several experimental systems, but the spatial overlap of these structures within the cell has precluded analysis of the putative long-range mechanisms by which MTs growing through the cell body reach FAs in the periphery of the cell. In the work described here cell geometry was controlled to remove the spatial overlap of cellular structures thus allowing for unambiguous observation of MT guidance.

Tomography and static-mechanical properties of adherent cells.

A tomography approach is used to reconstruct 3D cell shapes and, simultaneously, the shapes/positions of the nuclei within these cells. Subjecting the cells to well-defined microconfinements of various diameters allow for relating the steady-state shapes of cells to their static-mechanical properties. The observed shapes show striking regularities between different cell types and all fit to a model that takes into account the cell membrane, cortical actin, and the nucleus.

Carboxybetaine methacrylate polymers offer robust, long-term protection against cell adhesion.

Films of poly(carboxybetaine methacrylate), poly(CBMA), grafted onto microetched gold slides are effective in preventing nonspecific adhesion of cells of different types. The degree of adhesion resistance is comparable to that achieved with the self-assembled monolayers, SAMs, of oligo(ethylene glycol) alkanethiolates. In sharp contrast to the SAMs, however, substrates protected with poly(CBMA) can be stored in dry state without losing their protective properties for periods up to 2 weeks.

Antibacterial nanoparticle monolayers prepared on chemically inert surfaces by cooperative electrostatic adsorption (CELA).

Cooperative electrostatic adsorption (CELA) is used to deposit monolayer coatings of silver nanoparticles on relatively chemically inert polymers, polypropylene, and Tygon. Medically relevant components (tubing, vials, syringes) coated by this method exhibit antibacterial properties over weeks to months with the coatings being stable under constant-flow conditions. Antibacterial properties of the coatings are due to a slow release of Ag(+) from the particles.

The chemopreventive bioflavonoid apigenin inhibits prostate cancer cell motility through the focal adhesion kinase/Src signaling mechanism.

Prostate cancer mortality is primarily attributed to metastatic rather than primary, organ-confined disease. Acquiring a motile and invasive phenotype is an important step in development of tumors and ultimately metastasis. This step involves remodeling of the extracellular matrix and of cell-matrix interactions, cell movement mediated by the actin cytoskeleton, and activation of focal adhesion kinase (FAK)/Src signaling.

Nanoparticle-based solution deposition of gold films supporting bioresistant SAMs.

Thin films of gold on glass are prepared by solution deposition of functionalized gold nanoparticles followed by thermal treatment. The processed films adhere strongly to glass without any adhesion layers and can be micropatterned/microetched without delamination from the substrate. The formation of self-assembled monolayers (SAMs) of oligo(ethylene glycol) alkane thiols (EG SAMs) renders the films resistant to cell adhesion and allows for cell patterning.

Characterization and optimization of gold nanoparticle-based silver-enhanced immunoassays.

Silver-enhanced nanoparticle-labeled immunoassays provide a simple, low-cost, and effective way of detecting antigens in dilute solutions. The physical mechanisms behind their operation, however, have not been fully investigated. We present a semiquantitative approach for optimizing sandwich nanoparticle immunoassays using an adsorption-controlled kinetic model.