Peter C. Searson

The physics of cancer: the role of physical interactions and mechanical forces in metastasis

Metastasis is a complex, multistep process responsible for >90% of cancer-related deaths. In addition to genetic and external environmental factors, the physical interactions of cancer cells with their microenvironment, as well as their modulation by mechanical forces, are key determinants of the metastatic process. We reconstruct the metastatic process and describe the importance of key physical and mechanical processes at each step of the cascade. The emerging insight into these physical interactions may help to solve some long-standing questions in disease progression and may lead to new approaches to developing cancer diagnostics and therapies.

ZnO quantum particle thin films fabricated by electrophoretic deposition

Thin films of quantum size ZnO particles were fabricated by electrophoretic deposition from stable colloidal suspensions. The average particle size and hence the optical properties can be tailored by controlling the aging time and temperature of the suspensions. Thin films prepared by electrophoretic deposition exhibit optical properties characteristic of the quantum size particles. Both the band-to-band and visible photoluminescence were progressively blue shifted with decreasing particle size in the film.

A perinuclear actin cap regulates nuclear shape

Defects in nuclear morphology often correlate with the onset of disease, including cancer, progeria, cardiomyopathy, and muscular dystrophy. However, the mechanism by which a cell controls its nuclear shape is unknown. Here, we use adhesive micropatterned surfaces to control the overall shape of fibroblasts and find that the shape of the nucleus is tightly regulated by the underlying cell adhesion geometry. We found that this regulation occurs through a dome-like actin cap that covers the top of the nucleus. This cap is composed of contractile actin filament bundles containing phosphorylated myosin, which form a highly organized, dynamic, and oriented structure in a wide variety of cells. The perinuclear actin cap is specifically disorganized or eliminated by inhibition of actomyosin contractility and rupture of the LINC complexes, which connect the nucleus to the actin cap. The organization of this actin cap and its nuclear shape-determining function are disrupted in cells from mouse models of accelerated aging (progeria) and muscular dystrophy with distorted nuclei caused by alterations of A-type lamins. These results highlight the interplay between cell shape, nuclear shape, and cell adhesion mediated by the perinuclear actin cap.

Electrochemical deposition of metals onto silicon

The general concepts governing the electrochemical deposition of metal films onto semiconductors are discussed. Deposition onto semiconductor surfaces is complicated due to the band structure of the semiconductor, which affects both the thermodynamics and the kinetics of metal deposition processes. The influence of the potential distribution at the semiconductor/solution interface on the charge transfer mechanisms involved in deposition of metals is discussed. Models for electrochemical nucleation and growth are described and the influence of the unique physical properties of semiconductors is analysed. Finally, we present recent results for electrochemical deposition of gold, copper and platinum onto n-type silicon.

Influence of solvent on the growth of ZnO nanoparticles

We have synthesized ZnO nanoparticles by precipitation from zinc acetate in a series of n-alkanols from ethanol to 1-hexanol as a function of temperature. In this system, nucleation and growth are relatively fast and, at longer times, the average particle size continues to increase due to diffusion-limited coarsening. During coarsening, the particle volume increases linearly with time, in agreement with the Lifshitz-Slyozov-Wagner (LSW) model. The coarsening rate increases with increasing temperature for all solvents and increases with alkanol chain length. We show that the rate constant for coarsening is determined by the solvent viscosity, surface energy, and the bulk solubility of ZnO in the solvent.

State-of-the-art in design rules for drug delivery platforms: Lessons learned from FDA-approved nanomedicines

The ability to efficiently deliver a drug to a tumor site is dependent on a wide range of physiologically imposed design constraints. Nanotechnology provides the possibility of creating delivery vehicles where these design constraints can be decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing targeting efficiency and efficacy. Here we review the design strategies of the two FDA-approved antibody-drug conjugates (Brentuximab vedotin and Trastuzumab emtansine) and the four FDA-approved nanoparticle-based drug delivery platforms (Doxil, DaunoXome, Marqibo, and Abraxane) in the context of the challenges associated with systemic targeted delivery of a drug to a solid tumor. The lessons learned from these nanomedicines provide an important insight into the key challenges associated with the development of new platforms for systemic delivery of anti-cancer drugs.

Magnetic trapping and self-assembly of multicomponent nanowires

Magnetic nanowires suspended in fluid solutions can be assembled and ordered by taking advantage of their large shape anisotropy. Magnetic manipulation and assembly techniques are demonstrated, using electrodeposited Ni nanowires, with diameter 350 nm and length 12 μm. Orienting suspended nanowires in a small magnetic field H≈10 G promotes self-assembly of continuous chains that can extend over several hundred μm. The dynamics of this process can be described quantitatively in terms of the interplay of magnetic forces and fluid drag at low Reynolds number. In addition, a new technique of magnetic trapping is described, by which a single magnetic nanowire can be captured between lithographically patterned magnetic microelectrodes. The use of three-segment Pt–Ni–Pt nanowires yields low resistance, Ohmic electrical contacts between the nanowires and the electrodes. This technique has potential for use in the fabrication and measurement of nanoscale magnetic devices.

Polypyrrole Composite Electrodes in an All‐Polymer Battery System

The authors have fabricated an all-polymer battery utilizing the redox properties of electrically conducting polymers for the anode and cathode in conjunction with an ionic conducting polymer gel electrolyte. The anode and cathode consist of pyrrole electropolymerized onto a graphite fiber substrate resulting in a high-surface-area, composite electrode. A polymer gel electrolyte, based on polyacrylonitrile, was solution cast onto the electrodes to form an all-polymer cell. This system exhibits a specific charge capacity of 22 mAh/g based on the electroactive mass of the cathode and discharging the system to 0.4 V. These cells show no loss of capacity when cycled to 100 cycles.

Structural and magneto-transport properties of electrodeposited bismuth nanowires

Arrays of semimetallic Bi nanowires have been successfully fabricated by electrodeposition. Each nanowire consists of elongated Bi grains along the wire direction. Very large positive magnetoresistance of 300% at low temperatures and 70% at room temperature with quasilinear field dependence has been observed. These features are desirable for wide-range field sensing applications.

The blood-brain barrier: an engineering perspective

It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlichs first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and this selective permeability remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore, advances in our understanding of the structure and function of the blood-brain barrier are key to developing effective treatments for a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases.