New and Notable

Viral genomes are commonly pro-tected by capsids with beautiful geom-etries and symmetries. However,despite the relative simplicity of thecapsid shapes, many fundamentalquestions remain unanswered aboutcapsids mechanical properties andtheir self-assembly mechanisms,which, in turn, have important biolog-ical implications. Therefore, gainingdeeper insights into the nature of viralshells in particular, and nanoscaleshells in general, could provide foun-dations for further advances in a vari-ety of applications in nanomaterials,bioscience, and medicine.It has been well known since Crickand Watson’s groundbreaking articlein 1956 (1) that nearly-spherical shellsof small viruses, called capsids, arelikelytobecomposed ofidenticalmul-tiprotein units, called capsomers, witha total number that is a multiple of12, packed into a regular pseudo-crys-talline structure with icosahedral sym-metry. Capsomers are often found tobe~10nmindiameter.Therefore,con-ceptual understanding of capsid shapesand their mechanical properties shouldstart from the theory of thin elasticshells with icosahedral symmetry and,ideally,alsotakeintoaccounttheinter-nal mechano-chemical properties ofcapsomers.The classical, continuous theory ofthinelasticshells(2)servesasaconve-nient starting point for gaining insightsinto the way viral capsids deform un-der various mechanical stresses. Forexample, a ping-pong or a tennis ballmay be compressed in various ways(see Fig. 1 a)(2,3), under the load ofeither a rigid plane or a spatially local-ized object. When a rigid plane indentsthe shell, first the shell’s surface areain contact with the plane flattens, thenbuckles inwards at higher loads, mini-mizing its elastic energy (3). Thisbuckling is a first-order transition,showing hysteresis and irreversibilitywhen the deformations are large. Inthe opposite limit a sharp object maybe used to make an indentation, wherea circular fold appears at low loads(Fig. 1 a), with the extent of the defor-mation being proportional to theapplied force (3). Contrary to the caseof contact with a plane, this transitionis continuous and reversible. However,at higher loads, the fold further trans-forms into a polygonal structure,composed by a number of inflexibleridges (Fig. 1 a). Similar structuresbecome also energetically favored forlarge deformations by a rigid plane.Interestingly, the shape of the polygonfurther evolves as the load continuesto increase.The next step in understanding thenature of viral shells and their defor-mations is to recall that the capsidsurface is composed of capsomers asunits. In the simplest approximation,the mechanical network of the shellmay be locally characterized by elasticstretching and bending deformations.When the spherical topology is addi-tionally imposed, minimization ofthe network’s energy results in thecapsid’s icosahedral shape and deter-mines many of its mechanical proper-ties (4,5). This can be understoodin the following way: When a regularplanar triangular lattice is mappedonto a spherical surface, an excess ofvertices is produced. Therefore, toform a smooth lattice, it is necessaryto remove some of the originalplanar points or, in other words,to introduce so-called topologicaldefects. Introducing such defectsstrongly affects the elastic energy ofthe shell in the ground state (in partic-ular, increasing the stretching energy(4)). However, because the shell isflexible, some vertices buckle out ofthe plane to lower their energies byforming conical structures. Detailedcalculations show that increasingthe radius of the shell makes thesebucklings more favorable and sharper,leading to more faceted structures(Fig. 1 b)(4,5).When the local curvature becomescomparable to the capsomer size, forexample during strong deformations,the key assumptions of the theoryofelasticitymaynolongerhold.There-fore, the structural chemistry ofproteins comprising the capsomers,and the corresponding interproteininteractions, need to be taken intoaccount. Kononova and coworkers (6)combined single-molecule atomicforce microscopy technique with long-timescale biomolecular simulations todescribe the mechano-chemistry ofCowpeaChloroticMottleViruscapsid,investigating structural transitions andmechanisms when viral shells aremechanically deformed. During thepast decade, single-molecule atomic-force microscopy experiments andassociated molecular-dynamics simu-lations have become a powerful toolfor investigating folding-unfoldingprocesses of single proteins andmechanicalresponsesofmorecomplexbiomolecular assemblies (7,8).As noted above, a viral capsidis characterized by a complicatedmicroscopic structure, where the cap-sid’s mechanical properties dependon multiscale couplings across theshell, both in the neighborhoods ofindividual capsomers and involvinglarger-scale collective excitations.The relaxation processes followingcapsid deformations occur on milli-second-to-second timescales,requiringhigh-performance computational ap-proaches for their simulation. By using