Mutual repression ($\dot{x}=f(y)-x,\dot{y}=g(x)-y$)

Two components mutually repress when each inhibits the other's production. With decreasing $f,g$, the two negative interactions create a positive feedback loop. Sufficiently strong repression can produce two stable states: high $x$, low $y$, and the reverse.

// Target: mathematical-biology.bigb

For $\dot{x}=\lambda /(1+y^m)-x$, $\dot{y}=\lambda /(1+x^n)-y$, the equilibrium slope product is $K=mn{x}^n{y}^m/[(1+x^n)(1+y^m)]$. A value $K>1$ gives a saddle separating attracting alternatives. Both exponents greater than one allow this at sufficiently large common $\lambda$. If both are at most one it is impossible. If $0<m\le 1<n$, define $Y(x)$ as the unique positive solution of $Y^{-1}+Y^{m-1}=x^{-1}+x^{n-1}$ and set $K_{m,n}(x)=mn{x}^{n}Y(x{)}^m/[(1+x^n)(1+Y(x{)}^m)]$. All equilibria are parameterized by $\lambda =x(1+Y^m)$, whose derivative is $(1+Y^m)(1-K)/(1-m{Y}^m/(1+Y^m))$. Thus multistability for some common strength occurs exactly when ${\max }_{x>0}{K}_{m,n}(x)>1$. For $m=1$ the maximum is $(n-1{)}^2[(n+1)/(n-1){]}^{(n+1)/n}/(4n)$. Consequently $mn>1$ alone is not sufficient when the two synthesis strengths are required to coincide.

For positive $m,n$, this mutual repression system can display bistability for some $\lambda$ exactly when both $m>1$ and $n>1$. If either exponent is at most one, it has a unique stable equilibrium for every $\lambda$. To prove the less obvious case $m\le 1<n$, put $a=x/(1+x)$ and $b=y/(1+y)$ at equilibrium. Equality of the two expressions for $\lambda$ gives $a\le b(1-b{)}^{n-1}$. The loop gain is then bounded by $mn{b}^2(1-b{)}^{n-1}$, whose maximum is $4mn(n-1{)}^{n-1}/(n+1{)}^{n+1}<1$. Swap the two components for the other case. If both exponents exceed one, sufficiently large $\lambda$ yields two stable equilibria with $(x,y)\sim (\lambda ,{\lambda }^{1-m})$ and $(x,y)\sim ({\lambda }^{1-n},\lambda )$. The weaker condition $mn\le 1$ is sufficient to exclude multistability, but does not exhaust all exclusions when the same production prefactor is imposed.

// Target: mathematical-biology.bigb

At an equilibrium $x_{\ast }=f(y_{\ast })$, $y_{\ast }=g(x_{\ast })$, the Jacobian matrix has eigenvalues $-1\pm \sqrt{f^{\prime }(y_{\ast })g^{\prime }(x_{\ast })}$. Its product of repression gains is also $(\partial \log f/\partial \log y)(\partial \log g/\partial \log x)$. Product below one gives a stable node, above one a saddle, and equality the threshold for a zero eigenvalue. Robust multiple stable equilibria require an intervening unstable equilibrium; a gain exceeding one alone is not a sufficient global criterion for a particular pair of repression functions.

// Target: mathematical-biology.bigb