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I recently read a paper discussing how cells (primary mouse embryo fibroblasts) fail to spread and proliferate properly when plated on a soft substrate (i.e. soft PDMS pillars with stiffness k = 2.3 nN$\mu$m$^{-1}$), but spreading and proliferation can be restored with cyclic stretching of cells.

http://www.nature.com/ncomms/2015/150223/ncomms7333/full/ncomms7333.html

My question is if we understand why cells need to be on a hard surface to do normal operations (proliferate and spread)? It doesn't seem to me that a soft surface would be any more difficult for a cell to attach to. I would think that a "slippery" (I'm not sure of a correct biological term for this) surface may have this effect, but I wouldn't expect this from a soft surface.

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    $\begingroup$ Some cells need a matrix to adhere. Adherence relays proliferative signals in these cells. If you coat the PDMS pillars with polt-D-lysine or collagen then the cells may grow well. $\endgroup$ – WYSIWYG Sep 17 '15 at 18:14
  • $\begingroup$ Please keep in mind that this is about a single cell type (MEFs), and not extensible to all cell types and environments. $\endgroup$ – MattDMo Sep 17 '15 at 18:37
  • $\begingroup$ @WYSIWYG so are you saying that it's harder for cells to adhere to a softer substrate (or matrix)? for some reason, it's just not intuitive to me that that is true. $\endgroup$ – NaiveHalmos Sep 18 '15 at 19:02
  • $\begingroup$ @MattDMo is this not a general trend observed for most cell types? Am I way generalizing a result from one paper by thinking it would extend to most cells? I suppose fibroblasts don't typically need to move that much, but would you expect this result to hold for macrophages or any other cell that needs to move a lot? My apologies if these questions are too general -- my background is not in biology!! $\endgroup$ – NaiveHalmos Sep 18 '15 at 19:07
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    $\begingroup$ @NaiveHalmos it is not about being soft. Cells need some kind of interaction with the substrate. Some proteins allow this interaction because of their functional groups. This article says that hydroxyl groups in the substrate facilitates cell adhesion. $\endgroup$ – WYSIWYG Sep 18 '15 at 19:08
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As both @MattDMo and @WYSIWYG have already so succinctly answered this question in their comments I'm just going to attempt to expand a bit on their answers.

@MattDMo and @WYSIWYG have explained that the aforementioned paper from the question has results that are "not extensible to all cell types and environments" and "Some cells need a matrix to adhere. Adherence relays proliferative signals in these cells."

I'm just going to expand a little bit on these points... I know this addressing an erroneous assumption in the question rather than the question itself but bear with me.

Ok, so as has already been mentioned, different cell types in a multicellular eukaryote (like a mouse, or a human) only grow in certain environments and this is really important . Think about it like this, a mouse's body is made up of many different cell types all working together to create functional organs and systems and to ultimately make up the mouse. The individual cells don't know they are all coming together to make an entire animal and a cell is designed to grow and proliferate in order to make more copies of itself and spread. So why don't all cells just grow all over the place, on top of each other and spread to all parts of the body.

The reason you and the mouse aren't a formless mass of undifferentiated cells - like a big soft tumour - is because different cell types develop in such a manner that they can only grow in a restricted, structured way in a certain environment in your body. There are mechanical and chemical signals along with unique sets of growth factors that are found in different environments in the body that make it possible for certain cell types to grow in one area while not in another. It's why only blood cells can survive suspended in the blood not adhered to anything and your fibroblast cells (they make up your structured connective tissue can't, they need to adhere to a surface to grow. The different cell types only get their signal to keep growing when they are in their proper environment.

This is why when scientists are growing various mammalian cell cultures they have to be aware of what environment and growth factors the specific cell type they are working with requires in order to grow. Some mammalian (e.g. mouse) cells need a structured scaffold to grow them in culture and some can grow in soft or liquid culture.

Source: Hallmarks of Cancer: The Next Generation http://www.cell.com/cell/abstract/S0092-8674(11)00127-9?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867411001279%3Fshowall%3Dtrue [This is a classic paper that explains this far better than I can hope to - look for the section 'Sustaining Proliferative Signaling'.]

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