Adhesive Patterned Substrates for Stable Multicellular Arrangements

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Solution Overview

Problem

Current methods for creating multicellular arrangements in stable, stationary, and reproducible spatial configurations are limited, as they fail to control both cell-matrix and cell-cell interactions effectively, leading to cell migration and instability in tissue-like conditions.

Innovation Solution

The use of adhesive patterns with specific geometries on a plate, separated by non-adhesive areas, allows for controlled cell-matrix anchorage and oriented cell-cell contact, achieving mechanical equilibrium and reproducible conformation by ensuring cells do not migrate and maintain stable positions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If cells are isolated on adhesive patterns to control their shapes, then cell shape and internal organization become reproducible, but cells cannot establish cell-cell contacts which are necessary for tissue-like conditions

Engineering Contradiction:
Improvecell shape controlVSAvoidcell-cell interaction capability
Core Design Contradiction:
Manufacturing precisionVSAdaptability or versatility

Solution Approach 1:

The adhesive substrate is segmented into multiple distinct adhesive patterns (first adhesive pattern and second adhesive pattern) separated by a non-adhesive intercalating area. Each pattern can support individual cells while maintaining the ability for cells to interact across the non-adhesive boundary, thus achieving both shape control and cell-cell contact capability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The non-adhesive intercalating area serves as an intermediary element between adhesive patterns. It prevents cells from merging into a single confluent layer while still allowing controlled cell-cell interactions at the boundaries, mediating between the need for individual cell shape control and the need for tissue-like cell-cell contacts.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If cells are placed on adhesive patterns to enable cell-matrix contact, then cell anchorage is established, but cell positions become unstable and cells migrate due to intercellular interactions

Engineering Contradiction:
Improvecell anchorage stabilityVSAvoidcell position stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

By segmenting the adhesive substrate into separate adhesive patterns with non-adhesive areas between them, the invention creates discrete zones that anchor cells individually while preventing uncontrolled cell migration. The non-adhesive barriers restrict cell movement and establish stable positional relationships between cells on different patterns.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the substrate have different adhesive properties: adhesive patterns provide strong anchorage for individual cells, while non-adhesive intercalating areas provide resistance to cell migration. This local differentiation of adhesive quality enables both stable cell anchorage and stable cell positioning.

Inventive Principle:
Principle #3Local quality

3Shape

If larger adhesive patterns are used to accommodate multiple cells, then cell group shape control is achieved, but cell positions remain uncontrollable and cells move around each other

Engineering Contradiction:
Improvemulticellular arrangement shapeVSAvoidcell position stability
Core Design Contradiction:
ShapeVSStability of the object's composition

Solution Approach 1:

Instead of using a single large adhesive pattern, the invention segments the substrate into multiple smaller adhesive patterns separated by non-adhesive areas. This segmentation creates defined zones that control the shape of multicellular arrangements while the non-adhesive barriers prevent cells from moving freely between patterns, thus stabilizing cell positions.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The substrate exhibits local quality variations with adhesive regions providing cell anchorage and shape control, and non-adhesive regions providing positional stability by preventing cell migration. This spatial differentiation enables simultaneous achievement of shape control and position stability in multicellular arrangements.

Inventive Principle:
Principle #3Local quality

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enables the creation of mechanically stable and reproducible multicellular arrangements, allowing for controlled cell interactions and internal organization, mimicking physiological conditions, and facilitating applications in compound screening, diagnostics, and cellular therapy.

Implementation Method 1

adhesive patterns can be prepared by grafting extracellular matrix proteins on a solid support. Those proteins induce cellular adherence and promote cell attachment

Methodology Applied
Scientific EffectCell adhesion: Adhesive

Implementation Method 2

essentially non-adhesive intercalating area for preventing a cell on a first adhesive pattern to reach another adhesive pattern

Methodology Applied
Scientific EffectCytophobicity: Hydrophobe

Data Source

PatentEP2340302B1Methods and device to constrain multicellular arrangements in stable, stationary and reproducible spatial configuration
Publication Date: 2018.01.03 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • EP2340302B1 patent drawingFigure 1~4
  • EP2340302B1 patent drawingFigure 5
  • EP2340302B1 patent drawingFigure 5

AI summary

The present invention relates to methods and devices to obtain multicellular arrangements in stable, stationary and reproducible spatial configuration, and optionally with controled internal cell organisation, methods for preparing such devices, methods for studying the cells shapes, the cells architectures, the cells mechanical equilibrium, the cell- cell interaction, the cell movement and migration, the cell differentiation, the global internal cells organizations, the cells polarities and division, and/or any function of cells, methods for screening compounds of interest which enhance or inhibit specific cell functions.