Physics of a super-fast viral jab

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Most mechanical action in cells is generated by cytoskeletal molecular motors powered by ATP. A motor makes repetitive power stroke, each associated with a mechanochemical cycle, the duration of which cannot be accelerated, making resulting movements relatively slow. However, in nature, there are microscopic engines that are orders of magnitude faster than these cytoskeletal molecular motors: contractile injection protein systems. These are syringe-like molecular structures (1,2,3) that achieve high speeds by acting as irreversible one-shot machines that assemble before the contraction and disassemble after it.

The best-studied machine of this type is a bacteriophage tail (Fig. 1) consisting of three components—a sheath made of interlaced protein strands, a rigid hollow tube inside the sheath, and a baseplate. The key to the contractile action is the cylindrical sheath’s bistable state of two conformations—extended and contracted. The sheath is assembled around the rigid central tube in the extended state. Binding of the baseplate at the end of the tail to the target cell surface triggers a transformation of a hexagonal dome-shaped plate structure to a six-pointed star shape (4). This plate’s transformation, in turn, triggers the dramatic contraction of the sheath (Fig. 1); the sheath shortens to about one-third of its original length, resulting in the tail tube extending beneath the baseplate (4), which pushes the tube out through a hole in the baseplate into the target cell and injects phage genome into the host cell. Characteristic time- and length scales of the contraction are ms and tens of nm, respectively (4).

Figure 1.

Contraction of the molecular sheath. Pre- (left) and post- (right) contraction states of the sheath. In the middle, the transient contractile state of the sheath is shown with the contracted bottom, extended top, and propagating up wavefront in between. Note the changed shape of the baseplate that triggers the contraction and the changed angle of intersection between the warp and weft threads. Angles α and β correspond to a lower-energy stable state and a higher-energy metastable state, respectively.

Molecular machines of a similar architectural organization have been bioinformatically identified in hundreds of viruses, bacteria, and archaea (4). For example, Vibrio cholerae uses phage-like protein-translocation structures to inject toxins into target cells (5); other bacteria use phage-like sheaths to create a channel in the envelope of their competitors to dissipate the competitors’ protonmotive force (6).

Both pre- and postcontraction atomic structures of the sheath have been deciphered (1). The sheath is composed of several helical strands of protein gp18 spiraling around the central tube. The protein subunits are initially assembled into an interwoven mesh making a high-energy metastable structure, somewhat like an extended spring locked in the precontraction conformation by noncovalent interactions. Mechanically, the mesh of the sheath can be represented by two sets of interlaced “warp and weft” threads (6) (Fig. 1). The rearrangement of the baseplate pulls the gp18 subunits closer together so that the subunits interdigitate with each other, compacting the sheath structure, increasing the inter-subunit contact area and charged and polar interactions between the subunits by a fewfold (1,7). Geometrically, this compaction is equivalent to changing the pitch and twist of gp18 helices (2,6), which lowers the free energy, decreasing the height and increasing the radius of the cylindrical sheath (Fig. 1).

Two basic questions about the mechanics of the one-shot contractile injection are the following: does the sheath contract all at once, uniformly along its height, or does contraction propagate as a wave from the baseplate up? What mechanical parameters determine characteristic time- and length scales of the contraction? Early experiments hinted that the contraction propagates as a wave (3), but direct observations of this super-fast process remain elusive. Detailed molecular modeling (6) made inroads into the quantitative mechanics of the contractile injection, but such progress is hindered by the structural complexity of the sheath. An elegant coarse-grained model published in this issue of the Biophysical Journal started to shed light on the answers (8).

The model (8) considers the helical protein strands of the sheath as ribbon-like anisotropic elastic filaments immersed into a viscous biofluid. Crucially, the free energy of the noncovalent interactions between the crisscrossing strands depends on the angle of the warp and weft threads’ intersection so that the energy has a low minimum when the threads are more parallel to each other (corresponding to the postcontraction sheath) and another, higher local minimum when the threads are more perpendicular to each other (corresponding to the metastable precontraction state) (Fig. 1). The authors of (8) calculated the combined free energy as the sum of the elastic bending energy of the helical filaments and the double-welled noncovalent filament interaction energy, then computed the effective mechanical deformation force from the net energy and balanced this force by the viscous drag from the environment. Numerical solutions and scaling analysis of the resulting equation, which has a traveling-wave-like solution, revealed the answer to the first question: contraction propagates as a wave. Namely, in the contractile process, the bottom of the sheath is a wide and short cylindrical surface where the filaments crisscross almost parallel to each other, while the top is a narrow cylinder with almost perpendicular intersections of the warp and weft filaments. The effective elastic pulling across the wavefront kicks the filaments at the bottom of the precontraction part of the sheath into the energetically lower conformation, propagating the wave.

By using scaling analysis and relatively well-known parameters of the system, the authors of (8) estimate that the width of the wavefront is on the order of a few nm and that the wave speed is staggeringly fast, on the order of a thousand microns per second, so the whole contraction is over in less than a ms considering the ∼100-nm-long sheath. Lastly, the analysis predicts how the speed of the contraction wave scales with geometric, mechanical, and thermodynamic parameters of the system, which can be tested by comparing the molecular syringes in different cells and viruses.

This new understanding of the coarse-grained mechanics of the microscopic contractile injection systems will be invaluable for elucidating the molecular details of the process. The model is also relevant for other one-shot protein machines, such as the actin-bundle spring converting twist to extension in acrosomal reaction (9) and internalized flagella encased in the bacterial periplasmic space transducing conformational transitions into motile strokes in the spirochetes (10).

Author contributions

A.M. wrote this article.

Declaration of interests

The author declares no competing interests.

Editor: Jeremy Smith.