Built-in mechanical stress in viral shells.

Mechanical properties of biological molecular aggregates are essential to their function. A remarkable example are double-stranded DNA viruses such as the φ29 bacteriophage, that not only has to withstand pressures of tens of atmospheres exerted by the confined DNA, but also uses this stored elastic energy during DNA translocation into the host. Here we show that empty prolated φ29 bacteriophage proheads exhibit an intriguing anisotropic stiffness which behaves counterintuitively different from standard continuum elasticity predictions. By using atomic force microscopy, we find that the φ29 shells are approximately two-times stiffer along the short than along the long axis. This result can be attributed to the existence of a residual stress, a hypothesis that we confirm by coarse-grained simulations. This built-in stress of the virus prohead could be a strategy to provide extra mechanical strength to withstand the DNA compaction during and after packing and a variety of extracellular conditions, such as osmotic shocks or dehydration.

Nanoindentation of Isometric Viruses on Deterministically Corrugated Substrates.

It has been just over 100 years since inventor Joseph Coyle perfected the egg carton-a package format that has known very little changes since its first appearance ( Dhillon , S. B. C. Inventor Created Better Way to Carry Eggs. In The Globe and Mail Vancouver , 2013 ). In this article, we extend Coyle's old idea to the study of mechanical properties of viruses. Virus stiffness, strength, and breaking force obtained by force spectroscopy atomic force microscopy (AFM) provide the knowledge required for designing nanocontainers for applications in biotechnology and medicine, and for understanding the fundamentals of virus-host interaction such as virus translocation from one cellular compartment to another. In previous studies, virus particles adsorbed on flat surfaces from a physiological buffer were subjected to directional deformation by a known force exerted via a microscopic probe. The affinity between the virus shell and surface is required to be strong enough to anchor particles on the substrate while they are indented or imaged, yet sufficiently weak to preserve the native structure and interactions prior deformation. The specific question addressed here is whether an experimental scheme characterized by increased contact area and stable mechanical equilibrium under directional compression would provide a more reliable characterization than the traditional flat substrate approach.

Quantitative nanoscale electrostatics of viruses.

Electrostatics is one of the fundamental driving forces of the interaction between biomolecules in solution. In particular, the recognition events between viruses and host cells are dominated by both specific and non-specific interactions and the electric charge of viral particles determines the electrostatic force component of the latter. Here we probe the charge of individual viruses in liquid milieu by measuring the electrostatic force between a viral particle and the Atomic Force Microscope tip. The force spectroscopy data of co-adsorbed ϕ29 bacteriophage proheads and mature virions, adenovirus and minute virus of mice capsids is utilized for obtaining the corresponding density of charge for each virus. The systematic differences of the density of charge between the viral particles are consistent with the theoretical predictions obtained from X-ray structural data. Our results show that the density of charge is a distinguishing characteristic of each virus, depending crucially on the nature of the viral capsid and the presence/absence of the genetic material.

Cementing proteins provide extra mechanical stabilization to viral cages.

The study of virus shell stability is key not only for gaining insights into viral biological cycles but also for using viral capsids in materials science. The strength of viral particles depends profoundly on their structural changes occurring during maturation, whose final step often requires the specific binding of 'decoration' proteins (such as gpD in bacteriophage lambda) to the viral shell. Here we characterize the mechanical stability of gpD-free and gpD-decorated bacteriophage lambda capsids. The incorporation of gpD into the lambda shell imparts a major mechanical reinforcement that resists punctual deformations. We further interrogate lambda particle stability with molecular fatigue experiments that resemble the sub-lethal Brownian collisions of virus shells with macromolecules in crowded environments. Decorated particles are especially robust against collisions of a few kBT (where kB is the Boltzmann's constant and T is the temperature ~300 K), which approximate those anticipated from molecular insults in the environment.

Minimizing tip-sample forces in jumping mode atomic force microscopy in liquid.

Control and minimization of tip-sample interaction forces are imperative tasks to maximize the performance of atomic force microscopy. In particular, when imaging soft biological matter in liquids, the cantilever dragging force prevents identification of the tip-sample mechanical contact, resulting in deleterious interaction with the specimen. In this work we present an improved jumping mode procedure that allows detecting the tip-sample contact with high accuracy, thus minimizing the scanning forces (-100 pN) during the approach cycles. To illustrate this method we report images of human adenovirus and T7 bacteriophage particles which are prone to uncontrolled modifications when using conventional jumping mode.

The INCA system: a further step towards a telemedical artificial pancreas.

Biomedical engineering research efforts have accomplished another level of a "technological solution" for diabetes: an artificial pancreas to be used by patients and supervised by healthcare professionals at any time and place. Reliability of continuous glucose monitoring, availability of real-time programmable insulin pumps, and validation of safe and efficient control algorithms are critical components for achieving that goal. Nevertheless, the development and integration of these new technologies within a telemedicine system can be the basis of a future artificial pancreas. This paper introduces the concept, design, and evaluation of the "intelligent control assistant for diabetes, INCA" system. INCA is a personal digital assistant (PDA)-based personal smart assistant to provide patients with closed-loop control strategies (personal and remote loop), based on a real-time continuous glucose sensor (Guardian RT, Medtronic), an insulin pump (D-TRON, Disetronic Medical Systems), and a mobile general packet radio service (GPRS)-based telemedicine communication system. Patient therapeutic decision making is supervised by doctors through a multiaccess telemedicine central server that provides to diabetics and doctors a Web-based access to continuous glucose monitoring and insulin infusion data. The INCA system has been technically and clinically evaluated in two randomized and crossover clinical trials showing an improvement on glycaemic control of diabetic patients.