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Afundamental understanding of cell shaping with confined flexible filaments, including microtubules, actin filaments, and engineered nanotubes, has been limited by the complex interplay between the cell membrane and encapsulated filaments. Here, combining theoretical modeling and molecular dynamics simulations, we investigate the packing of an open or closed filament inside a vesicle. Depending on the relative stiffness and size of the filament to the vesicle as well as the osmotic pressure, the vesicle could evolve from an axisymmetric configuration to a general configuration with a maximum of three reflection planes, and the filament could bend in or out of plane or even coil up. A plethora of system morphologies are determined. Morphological phase diagrams predicting conditions of shape and symmetry transitions are established. Organization of actin filaments or bundles, microtubules, and nanotube rings inside vesicles, liposomes, or cells are discussed. Our results provide a theoretical basis to understand cell shaping and cellular stability and to help guide the development and design of artificial cells and biohybrid microrobots. [ABSTRACT FROM AUTHOR]

Nontypeable Haemophilus influenzae (NTHi) is a major cause of community acquired pneumonia and exacerbation of chronic obstructive pulmonary disease. A current effort in NTHi vaccine development has focused on generating humoral responses and has been greatly impeded by antigenic variation among the numerous circulating NTHi strains. In this study, we showed that pulmonary immunization of mice with killed NTHi generated broad protection against lung infection by different strains. While passive transfer of immune antibodies protected only against the homologous strain, transfer of immune T cells conferred protection against both homologous and heterologous strains. Further characterization revealed a strong Th17 response that was cross-reactive with different NTHi strains. Responding Th17 cells recognized both cytosolic and membrane-associated antigens, while immune antibodies preferentially responded to surface antigens and were highly strain specific. We further identified several conserved proteins recognized by lung Th17 cells during NTHi infection. Two proteins yielding the strongest responses were tested as vaccine candidates by immunization of mice with purified proteins plus an adjuvant. Immunization induced antigen-specific Th17 cells that recognized different strains and, upon adoptive transfer, conferred protection. Furthermore, immunized mice were protected against challenge with not only NTHi strains but also a fully virulent, encapsulated strain. Together, these results show that the immune mechanism of cross-protection against pneumonia involves Th17 cells, which respond to a broad spectrum of antigens, including those that are highly conserved among NTHi strains. These mechanistic insights suggest that inclusion of Th17 antigens in subunit vaccines offers the advantage of inducing broad protection and complements the current antibody-based approaches. [ABSTRACT FROM AUTHOR]