- Author:
- Kenneth Tran <k.tran@auckland.ac.nz>
- Date:
- 2017-08-31 15:35:06+12:00
- Desc:
- Adding online links.
- Permanent Source URI:
- https://models.cellml.org/workspace/4a2/rawfile/70c85f9bc526e95d066e088954387d87b82f72c9/XBModel.m
function [dy F_total ATPase F_net] = XBModel(t,y,Phase,Params)
% Get parameters
run Parameters_XBModel;
% Assign the state variables
Nxb = y(1); % Non-permissive fraction in overlap region
XBpreR = y(2); % Fraction of XBs in pre-rotated state (Stiffness generation)
XBpostR = y(3); % Fraction of XBS in post-rotated state (force generation)
x_XBpreR = y(4); % Strain of XBs in the pre-rotated state
x_XBpostR = y(5); % Strain of XBs in the post-rotated state
TropCaL = y(6); % Ca bound to the low affinity troponin site
TropCaH = y(7); % Ca bound to the high affinity troponin site
IntegF = y(8); % Integral of force
SL = y(9); % Sarcomere length
Afterload = Params(1); % Afterload for work-loop contraction
loop = Params(2); % Boolean to indicate if it is a work-loop contraction
preload_SL = Params(3); % Initial SL for work-loop contractions
T_loop(1) = Params(4); % Time for start of relaxation phasea (end of isotonic)
T_loop(2) = Params(5); % Tme for end of relaxation phase
passive = Params(6); % % Boolean for presence of passive force
% *****************************************************
% Specifying the three phases in the simulation
switch Phase
case 'isometric'
F_after = Afterload;
dSL = 0;
F_passive = passiveForces(SL,passive);
case 'isotonic'
F_after = Afterload;
dSL = (IntegF + viscosity*(SL_rest - SL))/mass;
F_passive = passiveForces(SL,passive);
end
% Prevent over extension
if SL > preload_SL
dSL = 0;
end
%% *****************************************************
% Ca binding to troponin
% Call function to get Ca
Cai = getCai(t); %uM
% convert pH to mM
H = 10^(-pH)*1e3; % H concentration in mM
% Ca binding to troponin C
konT = kon*1*Q_kon^((TmpC-37)/10);
konT_app = konT*(kdHCa^m + Href^m)/(kdHCa^m + H^m);
koffLT = koffL*1*1*Q_koff^((TmpC-37)/10); % Intact as opposed to skinned
koffHT = koffH*1*1*Q_koff^((TmpC-37)/10);
d_TropCaL = konT_app*Cai*(1-TropCaL) - koffLT*TropCaL;
d_TropCaH = konT_app*Cai*(1-TropCaH) - koffHT*TropCaH;
%% *****************************************************
% Thin filament activation rates
% Sarcomere geometry
sovr_ze = min(L_thick/2, SL/2);
sovr_cle = max(SL/2 - (SL-L_thin),L_hbare/2);
L_sovr = sovr_ze - sovr_cle; % Length of single overlap region
% Overlap fraction for thick filament
sov_thick = L_sovr*2/(L_thick - L_hbare);
% Overlap fraction for thin filament
sov_thin = L_sovr/L_thin;
TropReg = (1-sov_thin)*TropCaL + sov_thin*TropCaH;
permtot = (1/(1+(perm50/TropReg)^n_perm))^0.5;
permtot_p_n = min(100,1/permtot);
% Rate constants governing the transition btw Permissive and Non
kn_pT = kn_p*permtot*Q_kn_p^((TmpC-37)/10);
kp_nT = kp_n*permtot_p_n*Q_kp_n^((TmpC-37)/10);
%% *****************************************************
% Cross-bridge cycling rates
% Pxb to XBpreR
fappT = fapp*Xsp*Q_fapp^((TmpC-37)/10);
% Pi-dependent transition XBpreR to Pxb
gappslmd = 1 + (1-sov_thick)*gslmod;
gappT = gapp*gappslmd*Xsp*Q_gapp^((TmpC-37)/10);
gappT_true = gappT/Pi_ref; % True first order rate constant
% XBpreR to XBpostR
hfmd = exp(-sign(x_XBpreR)*hfmdc*(x_XBpreR/x0)^2);
hfT = hf*hfmd*Xsp*Q_hf^((TmpC-37)/10);
% H-dependent transition XBpostR to XBpreR
hbT = hb*Xsp*Q_hb^((TmpC-37)/10);
hbT_true = hbT/Href;
hbT_app = ((kdADP+MgADP_ref)/MgADP_ref)*(MgADP/(kdADP+MgADP))*hbT_true;
% MgATP-dependent transition from XBpostR to Pxb
if (x_XBpostR < x0)
gxbmd = exp(sigma_p*((x0-x_XBpostR)/x0)^2);
else
gxbmd = exp(sigma_n*((x0-x_XBpostR)/x0)^2);
end
gxbT = gxb*max(gxbmd,1)*Xsp*Q_gxb^((TmpC-37)/10);
gxbT_true = gxbT/MgATP_ref;
gxbT_app = ((kdADP+MgADP_ref)/(kdADP+MgADP))*gxbT_true;
% Pxb to XBpostR - Introduced for thermodynamic efficiency
G0 = -29600 + log(10)*R*(TmpC+273)*(-log10(1e-7));
K_MgATP = exp(-G0./(R.*(TmpC+273)))*1e6; % 1e6 to convert from M2 to mM2
fxbT = (kdADP*fappT*hfT*gxbT_true)/(gappT_true*hbT_true*K_MgATP);
fxb = (kdADP*fapp*hf*(gxb/MgATP_ref))/((gapp/Pi_ref)*(hb/Href)*K_MgATP); % Used for calculating max
ap1 = fappT;
ap2 = hfT;
ap3 = MgATP*gxbT_app;
am1 = Pi*gappT_true;
am2 = H*hbT_app;
am3 = fxbT;
%% *****************************************************
% Cross_bridge transitions
% Update all RUs
Pxb = 1 - Nxb - XBpreR - XBpostR;
d_Nxb = -kn_pT*Nxb + kp_nT*Pxb;
d_XBpreR = ap1*Pxb - am1*XBpreR - ap2*XBpreR + am2*XBpostR;
d_XBpostR = ap2*XBpreR + am3*Pxb - am2*XBpostR - ap3*XBpostR;
ATPase = rho*phi*sov_thick*(ap3*XBpostR - am3*Pxb);
%% *****************************************************
% Mean strain of strongly-bound states
% Steady State occupancies of the bound states - Duty fractions
Sum_duty = am3*am2 + ap3*ap1 + am2*ap1 + ap1*ap2 + am3*am1 + am3*ap2...
+ ap2*ap3 + am3*am1 + ap3*am1;
dutyPreR = (am3*am2 + ap3*ap1 + am2*ap1)/Sum_duty;
dutyPostR = (ap1*ap2 + am3*am1 + am3*ap2)/Sum_duty;
% No shortening during isotonic period
% This is to hold the SL at max contraction to get a loop
if (t>T_loop(1)) & (t<T_loop(2)) & loop
dSL = 0;
end
% Rate of change of the average distortions
d_x_XBpreR = dSL/2 + (Psi/dutyPreR)*(-ap1*x_XBpreR) + am2*(x_XBpostR-x0-x_XBpreR);
d_x_XBpostR = dSL/2 + (Psi/dutyPostR)*(ap2*(x_XBpreR + x0 - x_XBpostR));
% Compute the active force
F_active = sov_thick*(x_XBpreR*XBpreR + x_XBpostR*XBpostR);
% Maximal state occupancies under optimal conditions
max_XBpreR = (fapp*(hb+gxb)+fxb*fapp)/(gxb*hf + fapp*hf + gapp*hb + ...
gapp*gxb + fapp*hb + fapp*gxb + fxb*(hb+gapp+hb));
max_XBpostR = (fapp*hf+fxb*(gapp+hb))/(gxb*hf + fapp*hf + gapp*hb + ...
gapp*gxb + fapp*hb + fapp*gxb + fxb*(hb+gapp+hb));
% Factor to normalise force
FnormD = x0*max_XBpostR;
% Normalised Active force
Fnorm = F_active/FnormD;
% Normalised Passive force
F_passive = passiveForces(SL,passive);
% No shortening during isotonic period
% This is to hold the SL at max contraction to get a loop
if (t>T_loop(1)) & (t<T_loop(2)) & loop
dSL = 0;
end
% Difference in force
d_Force = F_after - Fnorm - F_passive;
% Total normalised force
F_total = Fnorm + F_passive;
% Used in Fevents script
F_net = F_total - F_after;
%% *****************************************************
% Assembling the derivative vector
dy = [d_Nxb; d_XBpreR; d_XBpostR; d_x_XBpreR;...
d_x_XBpostR; d_TropCaL; d_TropCaH; d_Force; dSL];
