Josiane Angèle Charlotte Smith-Clerc

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The Nano-Scale Mechanical Properties of the Extracellular Matrix Regulate Dermal Fibroblast Function

Lara Buscemi Estefanell, Boris Hinz, Jean-Jacques Meister, Josiane Angèle Charlotte Smith-Clerc

Changes in the mechanical properties of dermis occur during skin aging or tissue remodeling and affect the activity of resident fibroblasts. With the aim to establish elastic culture substrates that reproduce the variable softness of dermis, we determined Young's elastic modulus E of human dermis at the cell perception level using atomic force microscopy. The E of dermis ranged from 0.1 to 10 kPa, varied depending on body area and dermal layer, and tended to increase with age in 26-55-year-old donors. The activation state of human dermal fibroblasts cultured on "skin-soft" E (5 kPa) silicone culture substrates was compared with stiff plastic culture (GPa), collagen gel cultures (0.1-9 kPa), and fresh human dermal tissue. Fibroblasts cultured on skin-soft silicones displayed low mRNA levels of fibrosis-associated genes and increased expression of the matrix metalloproteinases (MMPs) MMP-1 and MMP-3 as compared with collagen gel and plastic cultures. The activation profile exhibited by fibroblasts on "skin-soft" silicone culture substrates was most comparable with that of human dermis than any other tested culture condition. Hence, providing biomimetic mechanical conditions generates fibroblasts that are more suitable to investigate physiologically relevant cell processes than fibroblasts spontaneously activated by stiff conventional culture surfaces.

Nature Publishing Group2014

The Single-Molecule Mechanics of the Latent TGF-beta 1 Complex

Lara Buscemi Estefanell, Aurélie Formey de Saint Louvent, Boris Hinz, Jean-Jacques Meister, David Ramonet Jimenez, Josiane Angèle Charlotte Smith-Clerc

Background: TGF-beta 1 controls many pathophysiological processes including tissue homeostasis, fibrosis, and cancer progression. Together with its latency-associated peptide (LAP), TGF-beta 1 binds to the latent TGF-beta 1-binding protein-1 (LTBP-1), which is part of the extracellular matrix (ECM). Transmission of cell force via integrins is one major mechanism to activate latent TGF-beta 1 from ECM stores. Latent TGF-beta 1 mechanical activation is more efficient with higher cell forces and ECM stiffening. However, little is known about the molecular events involved in this mechanical activation mechanism.

Elsevier2011

Josiane Angèle Charlotte Smith-Clerc

Actin Bundle Stabilization During Cell Spreading on Micropatterned Substrates

The Nano-Scale Mechanical Properties of the Extracellular Matrix Regulate Dermal Fibroblast Function

The Single-Molecule Mechanics of the Latent TGF-beta 1 Complex

The Nano-Scale Mechanical Properties of the Extracellular Matrix Regulate Dermal Fibroblast Function

Actin Bundle Stabilization During Cell Spreading on Micropatterned Substrates

The Single-Molecule Mechanics of the Latent TGF-beta 1 Complex