title: A general theoretical framework to infer endosomal network dynamics from quantitative image analysis.
abstract: BACKGROUND
  Endocytosis allows the import and distribution of cargo into a series of endosomes with distinct morphological and biochemical characteristics. Our current understanding of endocytic cargo trafficking is based on the kinetics of net cargo transport between endosomal compartments without considering individual endosomes. However, endosomes form a dynamic network of membranes undergoing fusion and fission, thereby continuously exchanging and redistributing cargo. The macroscopic kinetic properties, i.e., the properties of the endosomal network as a whole, result from the collective behaviors of many individual endosomes, a problem so far largely unaddressed.
  
  
  RESULTS
  Here, we developed a general theoretical framework to describe the dynamics of cargo distributions in the endosomal network. We combined the theory with quantitative experiments to study how the macroscopic kinetic properties of the endosomal network emerge from microscopic processes at the level of individual endosomes. We compared our theory predictions to experimental data in which dynamic distributions of endocytosed low-density lipoprotein (LDL) were quantified.
  
  
  CONCLUSIONS
  Our theory can quantitatively describe the observed cargo distributions as a function of time. Remarkably, the theory allows determining microscopic kinetic parameters such as the fusion rate between endosomes from still images of cargo distributions at different times of internalization. We show that this method is robust and sensitive because cargo distributions result from an average over many stochastic events in many cells. Our results provide theoretical and experimental support to the "funnel model" of endosome progression and suggest that the conversion of early to late endosomes is the major mode of LDL trafficking.
authors: Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Straβe 38, 01187 Dresden, Germany.
authors: Lionel
authors: L
authors: Foret
authors: Jonathan E
authors: JE
authors: Dawson
authors: Roberto
authors: R
authors: Villaseñor
authors: Claudio
authors: C
authors: Collinet
authors: Andreas
authors: A
authors: Deutsch
authors: Lutz
authors: L
authors: Brusch
authors: Marino
authors: M
authors: Zerial
authors: Yannis
authors: Y
authors: Kalaidzidis
authors: Frank
authors: F
authors: Jülicher
mesh_terms: D004705:Endocytosis; D011992:Endosomes / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D018613:Microscopy, Confocal; D008954:Models, Biological