title: Dynamics and Forces during Clathrin-Mediated Endocytosis
creator: Pennarola, Federica
subject: ddc-500
subject: 500 Natural sciences and mathematics
description: Biological cells use a process known as endocytosis to transport various types of extra- cellular cargo across their plasma membrane. Clathrin-Mediated Endocytosis (CME) is one of the main endocytic routes in eukaryotic cells, in which vesicle formation is mainly driven by the self-assembly of the clathrin cage and the adhesion energy of receptor-ligand bonds. In this thesis, I employed several bottom-up experimental approaches to investigate the dynamics, forces and coat curvatures involved in the CME of nanoscale particles at the ventral side of cells, probing the process with vary- ing levels of spatio-temporal control. In a first step, I combined surface chemistry techniques with nanoparticle (NP) technology and live-cell microscopy, to observe CME recruitment on surface-bound 200nm and 40nm NPs, either plain or coated with Transferrin, a ligand known to activate the pathway. We found that tuning NP size and chemistry induces significant changes in CME dynamics and recruitment statistics. I subsequently performed fluorescence nanoscopy measurements on the im- mobilized beads, and investigated whether clathrin-cage curvature adapts to varying cargo size. Notably, we found unexpected cage growth limitations with increasing NP diameter. Finally, by further integrating block-copolymer micellar nanolitography and DNA-based molecular tension sensors into the system, I investigated force generation during CME of NPs, and measured forces in the order of tens of pN during clathrin- coated vesicle formation and release into the cytosol. Together, these results further our understanding on how mechanical and molecular signatures of nanometric cargoes can be fine-tuned to gain entry into host cells through clathrin-mediated endocytosis.
date: 2026
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserver/37100/1/Pennarola_Federica_komplett.pdf
identifier: DOI:10.11588/heidok.00037100
identifier: urn:nbn:de:bsz:16-heidok-371000
identifier:   Pennarola, Federica  (2026) Dynamics and Forces during Clathrin-Mediated Endocytosis.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/37100/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng