Researchers created a library of micromolded, hexagonally spaced elastomeric micropost arrays, one to a few microns high, on which they cultivated cells.
The micropost system allowed engineers to modulate the rigidity and flexibility of the substrate surface without changing the adhesive or other material surface properties that could affect cell growth. Post height determined the degree to which a post would bend in response to a cell's horizontal traction force. The system enabled researchers to map cell traction forces to individ¬ual focal adhesions and spatially quantify sub-cellular distributions of focal-adhesion area, traction force and focal-adhesion stress.
The research, published in the current issue of the journal Nature Methods, demonstrated that the height of the posts determined the flexibility of the surface substrate, which in turn impacted the cell's morphology, leading to differences in focal adhesions, cytoskeletal contractility and stem-cell differentiation. Furthermore, early changes in cytoskeletal contractility measured by the devices predicted lineage fate decisions made days later by the stem cells.
"The library of micro¬post arrays spanned a more than 1,000-fold range of rigidity from 1.31 nN ìm−1 up to 1,556 nN ìm−1," said Chris Chen, lead author and the Skirkanich Professor of Innovation in Bioengineering in the School of Engineering and Applied Science at Penn. "Furthermore, the micropost array library will be made available to researchers in other laboratories."
Using current methods, it was not possible to change surface rigidity without also affecting other cellular properties such as the amount of active ligand molecules presented to cells, making it difficult to tease out the precise contributions of rigidity to cellular behavior.
Prior techniques employed the culture of cells on hydrogels derived from natural extracellular matrix proteins at different densities; however, changing densities of the gels impacted not only mechanical rigidity but also the amount of the binding or signaling ligand, leaving uncertainty as to the relevant contribution of these two matrix properties on the observed cellular response. Other synthetic hydrogels have been used that can vary rigidity without altering ligand density, but such systems cannot separate whether cells are sensing flexibility of individual molecules or of the macroscale mechanics.
"Although hydrogels will continue to be important in characterizing and controlling cell-material interactions, alternative approaches are necessary to understand how cells sense changes in substrate rigidity," Chen said.
In the body, cells do not exist in isolation but are in constant contact with other cells and with the extracellular matrix, providing structural support as well as both molecular and mechanical signals. In prior research, Chen's team has demonstrated that the push and pull of cellular forces drives the buckling, extension and contraction of cells during tissue development. These processes ultimately shape the architecture of tissues and play an important role in coordinating cell signaling, gene expression and behavior, and they are essential for wound healing and tissue homeostasis in adult organisms.
This study was conducted by Chen, Jianping Fu, Yang-Kao Wang, Michael T. Yang, Ravi A. Desai, Xiang Yu and Zhijun Liu of the Department of Bioengineering at Penn. Fu and Wang are now faculty members at the University of Michigan and the Skeletal-Joint Research Center of the National Cheng-Kung University Medical School.
The research was funded by grants from the National Institutes of Health, the National Science Foundation, the Army Research Office Multidisciplinary University Research Initiative, the Material Research Science and Engineering Center, the Institute for Regenerative Medicine, Penn's Nano/Bio Interface Center, the Center for Musculoskeletal Disorders of the University of Pennsylvania, the New Jersey Center for Biomaterials and the American Heart Association.
Jordan Reese | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy