Física de procesos celularesel papel de las escalas espaciales características de la membrana celular

  1. Beltran de Heredia Rodriguez, Elena
Dirigida por:
  1. Francisco Javier Cao García Director
  2. Francisco Monroy Muñoz Director

Universidad de defensa: Universidad Complutense de Madrid

Fecha de defensa: 30 de noviembre de 2018

Tribunal:
  1. Jesús Pérez Gil Presidente
  2. Iván López Montero Secretario
  3. Frederic Joubert Vocal
  4. Borja Ibarra Urruela Vocal
  5. Pedro Tarazona Lafarga Vocal
Departamento:
  1. Estructura de la Materia, Física Térmica y Electrónica

Tipo: Tesis

Resumen

The study of cells helps us understand how organisms function. In this thesis, we study the physics of cell constriction during division, cardiolipin sorting induced by membrane curvature, and phytoplankton size scaling with nutrient concentration. In all these cellular processes the effect of cell size and membrane curvature plays a major role. First, we study the mechanics of constriction during cell division using a model cell composed by a flexible membrane that encloses the cytoplasm. The optimal cell shapes along the constriction pathway are computed. These shapes can have prolate, oblate, or spherical lobes depending on membrane tension, pressure and on the constitutive parameters of the cell, size and spontaneous curvature. Analytical expressions are obtained for the main magnitudes of a symmetrically constricted cell as energy, constriction and stabilization forces, volume, and area. These analytic results are compared with the exact solution obtained from numerical computations, getting a good agreement for all quantities. For cells of micro size with flexible membranes, the constriction and stabilization forces are in the range of picoNewton, which is the range of forces practicable by bimolecular motors. We find that constriction force scales with the inverse of the cell size, that is, smaller cells require higher constriction forces. Finally, we study the stability and spontaneity of symmetric cell constriction. We obtain that stable symmetric constriction requires positive effective spontaneous curvature, while spontaneous constriction requires a spontaneous curvature higher than the characteristic inverse cell size. Next, we study the cardiolipin, CL, sorting induced by membrane curvature. CL is a cone-shaped lipid predominantly localized in highly curved membrane sites of bacteria and mitochondria. This localization has been argued to be geometry-driven since CL¿s conical shape relaxes the curvature frustration on these curved sites. Here, we test this hypothesis in experiments that isolate the effects of membrane curvature by using lipid-bilayer nanotubes of controlled radii pulled from cell-sized Giant Unilamellar Vesicles, GUVs, containing CL. CL-sorting is observed with increasing tube curvature, reaching a maximum at optimal CL-concentrations that vary with the tube radius. Our data are compatible with a thermodynamic model, from which a curvature of 1.1 nm to the -1 is predicted for CL, in agreement with previous estimates. A lateral cohesive interaction clustering into small domains of typically 10 CL molecules is also deduced from our results. Additionally, we find that CL molecules diffuse through the neck that connects the tube and the GUV, supporting the notion of fluidity for CL concomitant with self¿clustering. Finally, we study the phytoplankton size scaling with nutrient concentration. Phytoplankton, the autotrophic component of the plankton community, is a key factor in oceanic ecosystems and in biogeochemical cycling. Over much of the ocean, phytoplankton growth is limited by nitrate uptake. Based on previously published observations of marine species of phytoplankton, we obtain that phytoplankton dominant size r scales with S to the 0.85, where S is the ambient nitrate concentration in the ocean. Moreover, by combining a trait¿based uptake model with previous observations, we derive scaling relations for two phytoplankton traits: the porter number and the handling time. Our results indicate that handling time decreases with r to the -0.90, while porter number increases with r to the 1.56. All these works combine both theoretical and experimental approaches and contribute to a deeper quantitative understanding of the physical mechanisms underlying these cellular processes. The implications of these results are insightful in cell biology and span across different integrative areas of biology which involve Physical Chemistry, Mechanics, Biophysics, and Ecology.