Precisely parameterized experimental and computational models of tissue organization.

Area of Science:

• Biophysics
• Tissue Engineering
• Computational Biology

Background:

• Tissue organization and topology are crucial for function.
• Disorganized tissue morphology can lead to pathological remodeling.
• Analyzing tissue structure-function relationships requires precise methods.

Purpose of the Study:

• To develop a parameterized method for engineering complex tissue patterns.
• To investigate the relationship between cell organization and cardiac tissue function.
• To create mathematical models of cell function based on experimental patterns.

Main Methods:

• Designing geometrically complex, parameterized patterns to control cell alignment and communication.
• Guiding the growth of cardiac cell cultures using engineered patterns.
• Developing mathematical models correlating experimental patterns with cell function.

Main Results:

• Anisotropic patterned cardiac cultures showed similar local cell-cell interactions (confluency, morphology, connexin-43 expression) to isotropic cultures.
• Different anisotropic patterns, mimicking in vivo cardiac tissue alterations, produced variable functional responses.
• These variations have implications for the initiation and maintenance of cardiac arrhythmias.

Conclusions:

• Tissue geometry and topology dramatically affect cardiac function, independent of individual cell similarity.
• The proposed method offers a general strategy for experimentally and computationally investigating structure-function relationships in tissues.
• This approach can identify conditions where structural variations lead to impaired tissue function.