Large gaps exist in our understanding of how bacteriophages, the most abundant biological entities on Earth, assemble and function. The structure of the “neck” region, where the DNA-filled capsid is connected to the host-recognizing tail remains poorly understood. We describe cryo-EM structures of the neck, the neck-capsid and neck-tail junctions, and capsid of the
- Award ID(s):
- 1700531
- PAR ID:
- 10252117
- Date Published:
- Journal Name:
- American lutherie
- ISSN:
- 1041-7176
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Agrobacterium phage Milano. The Milano neck 1 protein connects the 12-fold symmetrical neck to a 5-fold vertex of the icosahedral capsid. Comparison of Milano neck 1 homologs leads to four proposed classes, likely evolved from the simplest one in siphophages to more complex ones in myo- and podophages. Milano neck is surrounded by the atypical collar, which covalently crosslinks the tail sheath to neck 1. The Milano capsid is decorated with three types of proteins, a minor capsid protein (mCP) and two linking proteins crosslinking the mCP to the major capsid protein. The extensive network of disulfide bonds within and between neck, collar, capsid and tail provides an exceptional structural stability to Milano. -
Membrane neck formation is essential for scission, which, as recent experiments on tubules have demonstrated, can be location dependent. The diversity of biological machinery that can constrict a neck such as dynamin, actin, ESCRTs and BAR proteins, and the range of forces and deflection over which they operate, suggest that the constriction process is functionally mechanical and robust to changes in biological environment. In this study, we used a mechanical model of the lipid bilayer to systematically investigate the influence of location, symmetry constraints, and helical forces on membrane neck constriction. Simulations from our model demonstrated that the energy barriers associated with constriction of a membrane neck are location-dependent. Importantly, if symmetry restrictions are relaxed, then the energy barrier for constriction is dramatically lowered and the membrane buckles at lower values of forcing parameters. Our simulations also show that constriction due to helical proteins further reduces the energy barrier for neck formation when compared to cylindrical proteins. These studies establish that despite different molecular mechanisms of neck formation in cells, the mechanics of constriction naturally leads to a loss of symmetry that can lower the energy barrier to constriction.more » « less
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Abstract This paper introduces a novel cable-driven robotic platform that enables six degrees-of-freedom (DoF) natural head–neck movements. Poor postural control of the head–neck can be a debilitating symptom of neurological disorders such as amyotrophic lateral sclerosis and cerebral palsy. Current treatments using static neck collars are inadequate, and there is a need to develop new devices to empower movements and facilitate physical rehabilitation of the head–neck. State-of-the-art neck exoskeletons using lower DoF mechanisms with rigid linkages are limited by their hard motion constraints imposed on head–neck movements. By contrast, the cable-driven robot presented in this paper does not constrain motion and enables wide-range, 6-DoF control of the head–neck. We present the mechatronic design, validation, and control implementations of this robot, as well as a human experiment to demonstrate a potential use case of this versatile robot for rehabilitation. Participants were engaged in a target reaching task while the robot applied both assistive and resistive moments on the head during the task. Our results show that neck muscle activation increased by 19% when moving the head against resistance and decreased by 28–43% when assisted by the robot. Overall, these results provide a scientific justification for further research in enabling movement and identifying personalized rehabilitation for motor training. Beyond rehabilitation, other applications such as applying force perturbations on the head to study sensory integration and applying traction to achieve pain relief may benefit from the innovation of this robotic platform which is capable of applying controlled 6-DoF forces/moments on the head.
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Abstract Purpose This study aimed to investigate the role of neck muscle activity and neck damping characteristics in traumatic brain injury (TBI) mechanisms.
Methods We used a previously validated head-neck finite element (FE) model that incorporates various components such as scalp, skull, cerebrospinal fluid, brain, muscles, ligaments, cervical vertebrae, and intervertebral discs. Impact scenarios included a Golf ball impact, NBDL linear acceleration, and Zhang’s linear and rotational accelerations. Three muscle activation strategies (no-activation, low-to-medium, and high activation levels) and two neck damping levels by perturbing intervertebral disc properties (high: hyper-viscoelastic and low: hyper-elastic) strategies were examined. We employed Head Injury Criterion (HIC), Brain Injury Criterion (BrIC), and maximum principal strain (MPS) as TBI measures.
Results Increased neck muscle activation consistently reduced the values of all TBI measures in Golf ball impact (HIC: 4%-7%, BrIC: 11%-25%, and MPS (occipital): 27%-50%) and NBDL study (HIC: 64%-69%, BrIC: 3%-9%, and MPS (occipital): 6%-19%) simulations. In Zhang’s study, TBI metric values decreased with the increased muscle activation from no-activation to low-to-medium (HIC: 74%-83%, BrIC: 27%-27%, and MPS (occipital): 60%-90%) and then drastically increased with further increases to the high activation level (HIC: 288%-507%, BrIC: 1%-25%, and MPS (occipital): 23%-305%). Neck damping changes from low to high decreased all values of TBI metrics, particularly in Zhang’s study (up to 40% reductions).
Conclusion Our results underscore the pivotal role of neck muscle activation and neck damping in TBI mitigation and holds promise to advance effective TBI prevention and protection strategies for diverse applications.
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