Photo-induced changes in tissue stiffness alter epithelial budding morphogenesis in the embryonic lung

Area of Science:

• Developmental Biology
• Biophysics
• Tissue Engineering

Background:

• Extracellular matrix (ECM) stiffness impacts progenitor cell differentiation in vitro.
• Tools to manipulate mechanical properties in intact embryonic organs are lacking.
• Previous photocrosslinking methods were limited to optically accessible tissues.

Purpose of the Study:

• To investigate the role of tissue stiffness in embryonic organ patterning and morphogenesis.
• To apply photocrosslinking to perturb mechanical properties within developing embryonic organs.
• To understand how changes in mesenchymal stiffness affect airway branching.

Main Methods:

• Photocrosslinking using Rose Bengal (RB) to stiffen the pulmonary mesenchyme of ex vivo cultured embryonic lungs.
• Assessing the impact of stiffened mesenchyme on FGF-10-mediated airway budding.
• Analyzing cell proliferation and apoptosis patterns.
• Utilizing a computational model of airway branching to elucidate budding mechanisms.

Main Results:

• Local photocrosslinking successfully stiffened the embryonic lung mesenchyme.
• Increased mesenchymal stiffness suppressed FGF-10-induced airway budding morphogenesis.
• Cell proliferation and apoptosis remained unaffected by the induced stiffness.
• Computational modeling indicated that FGF-10 buds form via growth-induced buckling, inhibited by increased stiffness.

Conclusions:

• Photocrosslinking can create regional mechanical property differences in intact embryonic organs.
• Tissue stiffness is a critical regulator of epithelial morphogenesis and patterning.
• This photocrosslinking technique is adaptable to various developing tissues and model systems.